The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Zhenfeng Duan - One of the best experts on this subject based on the ideXlab platform.
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transcriptional activation of cbfβ by cdk11p110 is necessary to promote osteosarcoma cell proliferation
Cell Communication and Signaling, 2019Co-Authors: Francis J Hornicek, Yong Feng, Jianming Zhang, Jacson Shen, Yunfei Liao, Zengwu Shao, Zhenfeng DuanAbstract:Aberrant expression of cyclin-dependent protein kinases (CDK) is a hallmark of cancer. CDK11 plays a crucial role in cancer cell growth and proliferation. However, the molecular mechanisms of CDK11 and CDK11 transcriptionally regulated genes are largely unknown. In this study, we performed a global transcriptional analysis using gene array technology to investigate the transcriptional role of CDK11 in osteosarcoma. The promoter luciferase assay, chromatin immunoprecipitation assay, and Gel Shift assay were used to identify direct transcriptional targets of CDK11. Clinical relevance and function of core-binding factor subunit beta (CBFβ) were further accessed in osteosarcoma. We identified a transcriptional role of protein-DNA interaction for CDK11p110, but not CDK11p58, in the regulation of CBFβ expression in osteosarcoma cells. The CBFβ promoter luciferase assay, chromatin immunoprecipitation assay, and Gel Shift assay confirmed that CBFβ is a direct transcriptional target of CDK11. High expression of CBFβ is associated with poor outcome in osteosarcoma patients. Expression of CBFβ contributes to the proliferation and metastatic behavior of osteosarcoma cells. These data establish CBFβ as a mediator of CDK11p110 dependent oncogenesis and suggest that targeting the CDK11- CBFβ pathway may be a promising therapeutic strategy for osteosarcoma treatment.
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abstract 1781 transcriptional activation of cbfβ by cdk11p110 is necessary to promote osteosarcoma cell proliferation
Cancer Research, 2019Co-Authors: Yong Feng, Francis J Hornicek, Zhenfeng DuanAbstract:Aberrant expression and activation of cyclin-dependent protein kinase (CDK) is a hallmark of cancer. CDK11 is a protein kinase in the CDK family and plays a crucial role in cancer cell growth and proliferation. However, the molecular mechanisms of CDK11 in osteosarcoma and CDK11 transcriptional regulated genes are largely unknown. In this study, we performed global transcriptional analysis using gene array technology to investigate the transcriptional role of CDK11 in osteosarcoma. The promoter luciferase assay, chromatin immunoprecipitation assay, and Gel Shift assay were used to identify direct transcriptional target of CDK11. Clinical significance relevance and function of CBFβ were further accessed in osteosarcoma tissue microarray and in osteosarcoma cell lines. We identified a transcriptional role of protein-DNA interaction for CDK11p110, but not CDK11p58, in the regulation of core-binding factor subunit beta (CBFβ) expression in osteosarcoma cells. The CBFβ promoter luciferase assay, chromatin immunoprecipitation assay, and Gel Shift assay confirmed that CBFβ is a direct transcriptional target of CDK11. High expression of CBFβ is associated with poor outcome in osteosarcoma patients. Expression of CBFβ contributes to the proliferation and metastatic behavior of osteosarcoma cells. These data establish CBFβas a mediator of CDK11p110dependent oncogenesis and suggest that targeting the CDK11-CBFβ pathway may be a promising therapeutic strategy for osteosarcoma treatment. Citation Format: Yong Feng, Francis Hornicek, Zhenfeng Duan. Transcriptional activation of CBFβ by CDK11p110 is necessary to promote osteosarcoma cell proliferation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1781.
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cyclin dependent kinase 11 cdk11 is required for ovarian cancer cell growth in vitro and in vivo and its inhibition causes apoptosis and sensitizes cells to paclitaxel
Molecular Cancer Therapeutics, 2016Co-Authors: Xianzhe Liu, Edwin Choy, Francis J Hornicek, Henry J. Mankin, Yan Gao, Jacson Shen, Wen Yang, Zhenfeng DuanAbstract:Ovarian cancer is currently the most lethal gynecologic malignancy with limited treatment options. Improved targeted therapies are needed to combat ovarian cancer. Here, we report the identification of cyclin-dependent kinase 11 (CDK11) as a mediator of tumor cell growth and proliferation in ovarian cancer cells. Although CDK11 has not been implicated previously in this disease, we have found that its expression is upregulated in human ovarian cancer tissues and associated with malignant progression. Metastatic and recurrent tumors have significantly higher CDK11 expression when compared with the matched, original primary tumors. RNAi-mediated CDK11 silencing by synthetic siRNA or lentiviral shRNA decreased cell proliferation and induced apoptosis in ovarian cancer cells. Moreover, CDK11 knockdown enhances the cytotoxic effect of paclitaxel to inhibit cell growth in ovarian cancer cells. Systemic in vivo administration of CDK11 siRNA reduced the tumor growth in an ovarian cancer xenograft model. Our findings suggest that CDK11 may be a promising therapeutic target for the treatment of ovarian cancer patients. Mol Cancer Ther; 15(7); 1691-701. ©2016 AACR.
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cyclin dependent kinase 11 cdk11 is crucial in the growth of liposarcoma cells
Cancer Letters, 2014Co-Authors: Edwin Choy, David C Harmon, Shunan Ye, Francis J Hornicek, Henry J. Mankin, Gregory M. Cote, Zhenfeng DuanAbstract:Liposarcoma is the second most common soft tissue sarcoma in adults, but treatment options have been quite limited thus far. In this study, we investigated the functional and therapeutic relevance of cyclin-dependent kinase 11 (CDK11) as a putative target in liposarcoma. CDK11 knockdown by synthetic siRNA or lentiviral shRNA decreased cell proliferation, and induced apoptosis in liposarcoma cells. Moreover, CDK11 knockdown enhances the cytotoxic effect of doxorubicin to inhibit cell growth in liposarcoma cells. These findings suggest that CDK11 is critical for the growth and proliferation of liposarcoma cells. CDK11 may be a promising therapeutic target for the treatment of liposarcoma patients.
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systematic kinome shrna screening identifies cdk11 pitslre kinase expression is critical for osteosarcoma cell growth and proliferation
Clinical Cancer Research, 2012Co-Authors: Zhenfeng Duan, David C Harmon, Edwin Choy, Henry J. Mankin, Xianzhe Liu, Jianming Zhang, Petur Nielsen, Nathanael S Gray, Francis J HornicekAbstract:Purpose: Identification of new targeted therapies is critical to improving the survival rate of patients with osteosarcoma. The goal of this study is to identify kinase based potential therapeutic target in osteosarcomas. Experimental Design: We used a lentiviral-based shRNA kinase library to screen for kinases which play a role in osteosarcoma cell survival. The cell proliferation assay was used to evaluate cell growth and survival. siRNA assays were applied to confirm the observed phenotypic changes resulting from the loss of kinase gene expression. CDK11 (PITSLRE) was identified as essential for the survival of osteosarcoma cells, and its expression was confirmed by Western blot analysis and immunohistochemistry. Overall patient survival was correlated with the CDK11 expression and its prognosis. The role of CDK11 expression in sustaining osteosarcoma growth was further evaluated in an osteosarcoma xenograft model in vivo . Results: Osteosarcoma cells display high levels of CDK11 expression. CDK11 expression knocked down by either lentiviral shRNA or siRNA inhibit cell growth and induce apoptosis in osteosarcoma cells. Immunohistochemical analysis showed that patients with osteosarcoma with high CDK11 tumor expression levels were associated with significantly shorter survival than patients with osteosarcoma with low level of tumor CDK11 expression. Systemic in vivo administration of in vivo ready siRNA of CDK11 reduced the tumor growth in an osteosarcoma subcutaneous xenograft model. Conclusions: We show that CDK11 signaling is essential in osteosarcoma cell growth and survival, further elucidating the regulatory mechanisms controlling the expression of CDK11 and ultimately develop a CDK11 inhibitor that may provide therapeutic benefit against osteosarcoma. Clin Cancer Res; 18(17); 4580–8. ©2012 AACR .
Francis J Hornicek - One of the best experts on this subject based on the ideXlab platform.
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transcriptional activation of cbfβ by cdk11p110 is necessary to promote osteosarcoma cell proliferation
Cell Communication and Signaling, 2019Co-Authors: Francis J Hornicek, Yong Feng, Jianming Zhang, Jacson Shen, Yunfei Liao, Zengwu Shao, Zhenfeng DuanAbstract:Aberrant expression of cyclin-dependent protein kinases (CDK) is a hallmark of cancer. CDK11 plays a crucial role in cancer cell growth and proliferation. However, the molecular mechanisms of CDK11 and CDK11 transcriptionally regulated genes are largely unknown. In this study, we performed a global transcriptional analysis using gene array technology to investigate the transcriptional role of CDK11 in osteosarcoma. The promoter luciferase assay, chromatin immunoprecipitation assay, and Gel Shift assay were used to identify direct transcriptional targets of CDK11. Clinical relevance and function of core-binding factor subunit beta (CBFβ) were further accessed in osteosarcoma. We identified a transcriptional role of protein-DNA interaction for CDK11p110, but not CDK11p58, in the regulation of CBFβ expression in osteosarcoma cells. The CBFβ promoter luciferase assay, chromatin immunoprecipitation assay, and Gel Shift assay confirmed that CBFβ is a direct transcriptional target of CDK11. High expression of CBFβ is associated with poor outcome in osteosarcoma patients. Expression of CBFβ contributes to the proliferation and metastatic behavior of osteosarcoma cells. These data establish CBFβ as a mediator of CDK11p110 dependent oncogenesis and suggest that targeting the CDK11- CBFβ pathway may be a promising therapeutic strategy for osteosarcoma treatment.
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abstract 1781 transcriptional activation of cbfβ by cdk11p110 is necessary to promote osteosarcoma cell proliferation
Cancer Research, 2019Co-Authors: Yong Feng, Francis J Hornicek, Zhenfeng DuanAbstract:Aberrant expression and activation of cyclin-dependent protein kinase (CDK) is a hallmark of cancer. CDK11 is a protein kinase in the CDK family and plays a crucial role in cancer cell growth and proliferation. However, the molecular mechanisms of CDK11 in osteosarcoma and CDK11 transcriptional regulated genes are largely unknown. In this study, we performed global transcriptional analysis using gene array technology to investigate the transcriptional role of CDK11 in osteosarcoma. The promoter luciferase assay, chromatin immunoprecipitation assay, and Gel Shift assay were used to identify direct transcriptional target of CDK11. Clinical significance relevance and function of CBFβ were further accessed in osteosarcoma tissue microarray and in osteosarcoma cell lines. We identified a transcriptional role of protein-DNA interaction for CDK11p110, but not CDK11p58, in the regulation of core-binding factor subunit beta (CBFβ) expression in osteosarcoma cells. The CBFβ promoter luciferase assay, chromatin immunoprecipitation assay, and Gel Shift assay confirmed that CBFβ is a direct transcriptional target of CDK11. High expression of CBFβ is associated with poor outcome in osteosarcoma patients. Expression of CBFβ contributes to the proliferation and metastatic behavior of osteosarcoma cells. These data establish CBFβas a mediator of CDK11p110dependent oncogenesis and suggest that targeting the CDK11-CBFβ pathway may be a promising therapeutic strategy for osteosarcoma treatment. Citation Format: Yong Feng, Francis Hornicek, Zhenfeng Duan. Transcriptional activation of CBFβ by CDK11p110 is necessary to promote osteosarcoma cell proliferation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1781.
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cyclin dependent kinase 11 cdk11 is required for ovarian cancer cell growth in vitro and in vivo and its inhibition causes apoptosis and sensitizes cells to paclitaxel
Molecular Cancer Therapeutics, 2016Co-Authors: Xianzhe Liu, Edwin Choy, Francis J Hornicek, Henry J. Mankin, Yan Gao, Jacson Shen, Wen Yang, Zhenfeng DuanAbstract:Ovarian cancer is currently the most lethal gynecologic malignancy with limited treatment options. Improved targeted therapies are needed to combat ovarian cancer. Here, we report the identification of cyclin-dependent kinase 11 (CDK11) as a mediator of tumor cell growth and proliferation in ovarian cancer cells. Although CDK11 has not been implicated previously in this disease, we have found that its expression is upregulated in human ovarian cancer tissues and associated with malignant progression. Metastatic and recurrent tumors have significantly higher CDK11 expression when compared with the matched, original primary tumors. RNAi-mediated CDK11 silencing by synthetic siRNA or lentiviral shRNA decreased cell proliferation and induced apoptosis in ovarian cancer cells. Moreover, CDK11 knockdown enhances the cytotoxic effect of paclitaxel to inhibit cell growth in ovarian cancer cells. Systemic in vivo administration of CDK11 siRNA reduced the tumor growth in an ovarian cancer xenograft model. Our findings suggest that CDK11 may be a promising therapeutic target for the treatment of ovarian cancer patients. Mol Cancer Ther; 15(7); 1691-701. ©2016 AACR.
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cyclin dependent kinase 11 cdk11 is crucial in the growth of liposarcoma cells
Cancer Letters, 2014Co-Authors: Edwin Choy, David C Harmon, Shunan Ye, Francis J Hornicek, Henry J. Mankin, Gregory M. Cote, Zhenfeng DuanAbstract:Liposarcoma is the second most common soft tissue sarcoma in adults, but treatment options have been quite limited thus far. In this study, we investigated the functional and therapeutic relevance of cyclin-dependent kinase 11 (CDK11) as a putative target in liposarcoma. CDK11 knockdown by synthetic siRNA or lentiviral shRNA decreased cell proliferation, and induced apoptosis in liposarcoma cells. Moreover, CDK11 knockdown enhances the cytotoxic effect of doxorubicin to inhibit cell growth in liposarcoma cells. These findings suggest that CDK11 is critical for the growth and proliferation of liposarcoma cells. CDK11 may be a promising therapeutic target for the treatment of liposarcoma patients.
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systematic kinome shrna screening identifies cdk11 pitslre kinase expression is critical for osteosarcoma cell growth and proliferation
Clinical Cancer Research, 2012Co-Authors: Zhenfeng Duan, David C Harmon, Edwin Choy, Henry J. Mankin, Xianzhe Liu, Jianming Zhang, Petur Nielsen, Nathanael S Gray, Francis J HornicekAbstract:Purpose: Identification of new targeted therapies is critical to improving the survival rate of patients with osteosarcoma. The goal of this study is to identify kinase based potential therapeutic target in osteosarcomas. Experimental Design: We used a lentiviral-based shRNA kinase library to screen for kinases which play a role in osteosarcoma cell survival. The cell proliferation assay was used to evaluate cell growth and survival. siRNA assays were applied to confirm the observed phenotypic changes resulting from the loss of kinase gene expression. CDK11 (PITSLRE) was identified as essential for the survival of osteosarcoma cells, and its expression was confirmed by Western blot analysis and immunohistochemistry. Overall patient survival was correlated with the CDK11 expression and its prognosis. The role of CDK11 expression in sustaining osteosarcoma growth was further evaluated in an osteosarcoma xenograft model in vivo . Results: Osteosarcoma cells display high levels of CDK11 expression. CDK11 expression knocked down by either lentiviral shRNA or siRNA inhibit cell growth and induce apoptosis in osteosarcoma cells. Immunohistochemical analysis showed that patients with osteosarcoma with high CDK11 tumor expression levels were associated with significantly shorter survival than patients with osteosarcoma with low level of tumor CDK11 expression. Systemic in vivo administration of in vivo ready siRNA of CDK11 reduced the tumor growth in an osteosarcoma subcutaneous xenograft model. Conclusions: We show that CDK11 signaling is essential in osteosarcoma cell growth and survival, further elucidating the regulatory mechanisms controlling the expression of CDK11 and ultimately develop a CDK11 inhibitor that may provide therapeutic benefit against osteosarcoma. Clin Cancer Res; 18(17); 4580–8. ©2012 AACR .
Edwin Choy - One of the best experts on this subject based on the ideXlab platform.
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androgen receptor is a potential novel prognostic marker and oncogenic target in osteosarcoma with dependence on cdk11
Scientific Reports, 2017Co-Authors: Yunfei Liao, Edwin Choy, Gregory M. Cote, Yong Feng, Yan Gao, Jacson Shen, Slim Sassi, Stefan Halvorsen, David C HarmonAbstract:Osteosarcoma is the most common bone cancer in children and adolescents. Previously, we have found that cyclin-dependent kinase 11 (CDK11) signaling was essential for osteosarcoma cell growth and survival. Subsequently, CDK11 siRNA gene targeting, expression profiling, and network reconstruction of differentially expressed genes were performed between CDK11 knock down and wild type osteosarcoma cells. Reconstructed network of the differentially expressed genes pointed to the AR as key to CDK11 signaling in osteosarcoma. CDK11 increased transcriptional activation of AR gene in osteosarcoma cell lines. AR protein was highly expressed in various osteosarcoma cell lines and patient tumor tissues. Tissue microarray analysis showed that the disease-free survival rate for patients with high-expression of AR was significantly shorter than for patients with low-expression of AR. In addition, AR gene expression knockdown via siRNA greatly inhibited cell growth and viability. Similar results were found in osteosarcoma cells treated with AR inhibitor. These findings suggest that CDK11 is involved in the regulation of AR pathway and AR can be a potential novel prognostic marker and therapeutic target for osteosarcoma treatment.
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cyclin dependent kinase 11 cdk11 is required for ovarian cancer cell growth in vitro and in vivo and its inhibition causes apoptosis and sensitizes cells to paclitaxel
Molecular Cancer Therapeutics, 2016Co-Authors: Xianzhe Liu, Edwin Choy, Francis J Hornicek, Henry J. Mankin, Yan Gao, Jacson Shen, Wen Yang, Zhenfeng DuanAbstract:Ovarian cancer is currently the most lethal gynecologic malignancy with limited treatment options. Improved targeted therapies are needed to combat ovarian cancer. Here, we report the identification of cyclin-dependent kinase 11 (CDK11) as a mediator of tumor cell growth and proliferation in ovarian cancer cells. Although CDK11 has not been implicated previously in this disease, we have found that its expression is upregulated in human ovarian cancer tissues and associated with malignant progression. Metastatic and recurrent tumors have significantly higher CDK11 expression when compared with the matched, original primary tumors. RNAi-mediated CDK11 silencing by synthetic siRNA or lentiviral shRNA decreased cell proliferation and induced apoptosis in ovarian cancer cells. Moreover, CDK11 knockdown enhances the cytotoxic effect of paclitaxel to inhibit cell growth in ovarian cancer cells. Systemic in vivo administration of CDK11 siRNA reduced the tumor growth in an ovarian cancer xenograft model. Our findings suggest that CDK11 may be a promising therapeutic target for the treatment of ovarian cancer patients. Mol Cancer Ther; 15(7); 1691-701. ©2016 AACR.
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cyclin dependent kinase 11 cdk11 is crucial in the growth of liposarcoma cells
Cancer Letters, 2014Co-Authors: Edwin Choy, David C Harmon, Shunan Ye, Francis J Hornicek, Henry J. Mankin, Gregory M. Cote, Zhenfeng DuanAbstract:Liposarcoma is the second most common soft tissue sarcoma in adults, but treatment options have been quite limited thus far. In this study, we investigated the functional and therapeutic relevance of cyclin-dependent kinase 11 (CDK11) as a putative target in liposarcoma. CDK11 knockdown by synthetic siRNA or lentiviral shRNA decreased cell proliferation, and induced apoptosis in liposarcoma cells. Moreover, CDK11 knockdown enhances the cytotoxic effect of doxorubicin to inhibit cell growth in liposarcoma cells. These findings suggest that CDK11 is critical for the growth and proliferation of liposarcoma cells. CDK11 may be a promising therapeutic target for the treatment of liposarcoma patients.
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systematic kinome shrna screening identifies cdk11 pitslre kinase expression is critical for osteosarcoma cell growth and proliferation
Clinical Cancer Research, 2012Co-Authors: Zhenfeng Duan, David C Harmon, Edwin Choy, Henry J. Mankin, Xianzhe Liu, Jianming Zhang, Petur Nielsen, Nathanael S Gray, Francis J HornicekAbstract:Purpose: Identification of new targeted therapies is critical to improving the survival rate of patients with osteosarcoma. The goal of this study is to identify kinase based potential therapeutic target in osteosarcomas. Experimental Design: We used a lentiviral-based shRNA kinase library to screen for kinases which play a role in osteosarcoma cell survival. The cell proliferation assay was used to evaluate cell growth and survival. siRNA assays were applied to confirm the observed phenotypic changes resulting from the loss of kinase gene expression. CDK11 (PITSLRE) was identified as essential for the survival of osteosarcoma cells, and its expression was confirmed by Western blot analysis and immunohistochemistry. Overall patient survival was correlated with the CDK11 expression and its prognosis. The role of CDK11 expression in sustaining osteosarcoma growth was further evaluated in an osteosarcoma xenograft model in vivo . Results: Osteosarcoma cells display high levels of CDK11 expression. CDK11 expression knocked down by either lentiviral shRNA or siRNA inhibit cell growth and induce apoptosis in osteosarcoma cells. Immunohistochemical analysis showed that patients with osteosarcoma with high CDK11 tumor expression levels were associated with significantly shorter survival than patients with osteosarcoma with low level of tumor CDK11 expression. Systemic in vivo administration of in vivo ready siRNA of CDK11 reduced the tumor growth in an osteosarcoma subcutaneous xenograft model. Conclusions: We show that CDK11 signaling is essential in osteosarcoma cell growth and survival, further elucidating the regulatory mechanisms controlling the expression of CDK11 and ultimately develop a CDK11 inhibitor that may provide therapeutic benefit against osteosarcoma. Clin Cancer Res; 18(17); 4580–8. ©2012 AACR .
Yong Feng - One of the best experts on this subject based on the ideXlab platform.
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transcriptional activation of cbfβ by cdk11p110 is necessary to promote osteosarcoma cell proliferation
Cell Communication and Signaling, 2019Co-Authors: Francis J Hornicek, Yong Feng, Jianming Zhang, Jacson Shen, Yunfei Liao, Zengwu Shao, Zhenfeng DuanAbstract:Aberrant expression of cyclin-dependent protein kinases (CDK) is a hallmark of cancer. CDK11 plays a crucial role in cancer cell growth and proliferation. However, the molecular mechanisms of CDK11 and CDK11 transcriptionally regulated genes are largely unknown. In this study, we performed a global transcriptional analysis using gene array technology to investigate the transcriptional role of CDK11 in osteosarcoma. The promoter luciferase assay, chromatin immunoprecipitation assay, and Gel Shift assay were used to identify direct transcriptional targets of CDK11. Clinical relevance and function of core-binding factor subunit beta (CBFβ) were further accessed in osteosarcoma. We identified a transcriptional role of protein-DNA interaction for CDK11p110, but not CDK11p58, in the regulation of CBFβ expression in osteosarcoma cells. The CBFβ promoter luciferase assay, chromatin immunoprecipitation assay, and Gel Shift assay confirmed that CBFβ is a direct transcriptional target of CDK11. High expression of CBFβ is associated with poor outcome in osteosarcoma patients. Expression of CBFβ contributes to the proliferation and metastatic behavior of osteosarcoma cells. These data establish CBFβ as a mediator of CDK11p110 dependent oncogenesis and suggest that targeting the CDK11- CBFβ pathway may be a promising therapeutic strategy for osteosarcoma treatment.
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abstract 1781 transcriptional activation of cbfβ by cdk11p110 is necessary to promote osteosarcoma cell proliferation
Cancer Research, 2019Co-Authors: Yong Feng, Francis J Hornicek, Zhenfeng DuanAbstract:Aberrant expression and activation of cyclin-dependent protein kinase (CDK) is a hallmark of cancer. CDK11 is a protein kinase in the CDK family and plays a crucial role in cancer cell growth and proliferation. However, the molecular mechanisms of CDK11 in osteosarcoma and CDK11 transcriptional regulated genes are largely unknown. In this study, we performed global transcriptional analysis using gene array technology to investigate the transcriptional role of CDK11 in osteosarcoma. The promoter luciferase assay, chromatin immunoprecipitation assay, and Gel Shift assay were used to identify direct transcriptional target of CDK11. Clinical significance relevance and function of CBFβ were further accessed in osteosarcoma tissue microarray and in osteosarcoma cell lines. We identified a transcriptional role of protein-DNA interaction for CDK11p110, but not CDK11p58, in the regulation of core-binding factor subunit beta (CBFβ) expression in osteosarcoma cells. The CBFβ promoter luciferase assay, chromatin immunoprecipitation assay, and Gel Shift assay confirmed that CBFβ is a direct transcriptional target of CDK11. High expression of CBFβ is associated with poor outcome in osteosarcoma patients. Expression of CBFβ contributes to the proliferation and metastatic behavior of osteosarcoma cells. These data establish CBFβas a mediator of CDK11p110dependent oncogenesis and suggest that targeting the CDK11-CBFβ pathway may be a promising therapeutic strategy for osteosarcoma treatment. Citation Format: Yong Feng, Francis Hornicek, Zhenfeng Duan. Transcriptional activation of CBFβ by CDK11p110 is necessary to promote osteosarcoma cell proliferation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1781.
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androgen receptor is a potential novel prognostic marker and oncogenic target in osteosarcoma with dependence on cdk11
Scientific Reports, 2017Co-Authors: Yunfei Liao, Edwin Choy, Gregory M. Cote, Yong Feng, Yan Gao, Jacson Shen, Slim Sassi, Stefan Halvorsen, David C HarmonAbstract:Osteosarcoma is the most common bone cancer in children and adolescents. Previously, we have found that cyclin-dependent kinase 11 (CDK11) signaling was essential for osteosarcoma cell growth and survival. Subsequently, CDK11 siRNA gene targeting, expression profiling, and network reconstruction of differentially expressed genes were performed between CDK11 knock down and wild type osteosarcoma cells. Reconstructed network of the differentially expressed genes pointed to the AR as key to CDK11 signaling in osteosarcoma. CDK11 increased transcriptional activation of AR gene in osteosarcoma cell lines. AR protein was highly expressed in various osteosarcoma cell lines and patient tumor tissues. Tissue microarray analysis showed that the disease-free survival rate for patients with high-expression of AR was significantly shorter than for patients with low-expression of AR. In addition, AR gene expression knockdown via siRNA greatly inhibited cell growth and viability. Similar results were found in osteosarcoma cells treated with AR inhibitor. These findings suggest that CDK11 is involved in the regulation of AR pathway and AR can be a potential novel prognostic marker and therapeutic target for osteosarcoma treatment.
Tsehung Huang - One of the best experts on this subject based on the ideXlab platform.
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monospecific antibody targeting of CDH11 inhibits epithelial to mesenchymal transition and represses cancer stem cell like phenotype by up regulating mir 335 in metastatic breast cancer in vitro and in vivo
BMC Cancer, 2019Co-Authors: Wenchien Huang, Oluwaseun Adebayo Bamodu, Peter Muhsin Chang, Tsuyi Chao, Tsehung Huang, Jiahong ChenAbstract:Metastasis is a leading cause of breast cancer mortality. The induction of epithelial-to-mesenchymal transition (EMT) and complex oncogenic signaling is a vital step in the evolution of highly metastatic and therapeutically-intractable breast cancer; necessitating novel target discovery or development of therapeutics that target metastatic breast cells (MBCs). To achieve this, this study employs a combination of in silico bioinformatics analyses, protein and transcript analyses, drug sensitivity assays, functional assays and animal studies. The present study identified CDH11 as an inductor and/or facilitator of metastatic signaling, and biomarker of poor prognosis in MBCs. Furthermore, we showed that in the presence of CDH11-rich cancer-associated fibroblasts (CAFs), MCF7 and MDA-MB-231 MBC cell lines acquired enhanced metastatic phenotype with increased CDH11, β-catenin, vimentin, and fibronectin (FN) expression. We also demonstrated, for the first time to the best of our knowledge that exposure to anti-CDH11 antibody suppresses metastasis, reduces CDH11, FN and β-catenin expression, and abrogate the cancer stem cell (CSC)-like traits of MBC cells. Interestingly, ectopic expression of miR-335 suppressed CDH11, β-catenin and vimentin expression, in concert with attenuated metastatic and CSC potentials of the MBC cells; conversely, inhibition of miR-335 resulted in increased metastatic potential. Finally, corroborating the in silica and in vitro findings, in vivo assays showed that the administration of anti-CDH11 antibody or miR-335 mimic suppressed tumorigenesis and inhibited cancer metastasis. These findings validate our hypotheses that miR-335 mediates anti-CDH11 antibody therapy response and that an enhanced miR-335/CDH11 ratio elicits marked suppression of the MBC CSC-like and metastatic phenotypes, thus revealing a therapeutically-exploitable inverse correlation between CDH11-enhanced CSC-like and metastatic phenotype and miR-335 expression in MBCs. Thus, we highlight the therapeutic promise of humanized anti-CDH11 antibodies or miR-335-mimic, making a case for their clinical application as efficacious therapeutic option in patients with MBC.