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Stefan Broer - One of the best experts on this subject based on the ideXlab platform.
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Novel Chemical Scaffolds to Inhibit the Neutral Amino Acid Transporter B0AT1 (SLC6A19), a Potential Target to Treat Metabolic Diseases.
Frontiers in Pharmacology, 2020Co-Authors: Aditya Yadav, Nishank Shah, Praveen Kumar Tiwari, Kiran Javed, Qi Cheng, Indrapal Singh Aidhen, Stefan BroerAbstract:Lack of B0AT1 (SLC6A19) partially protects mice against the onset of non-alcoholic steatohepatitis (NASH). To achieve a similar outcome through pharmacological treatment, we improved previously identified inhibitors of B0AT1 by medicinal chemistry and identified second generation inhibitors by high through-put screening. Modified diarylmethine compounds inhibited B0AT1 with IC50 values ranging from 8-90 μM. A second generation of inhibitors was derived from high-throughput screening and showed higher affinity (IC50 of 1-15 μM) and strong selectivity against amino acid transporters with similar substrate specificity, such as ASCT2 (SLC1A5) and LAT1 (SLC7A5). All compounds were unrelated to B0AT1 substrates but were likely to bind in the vicinity of the substrate binding site.
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Ablation of the ASCT2 (SLC1A5) gene encoding a neutral amino acid transporter reveals transporter plasticity and redundancy in cancer cells.
Journal of Biological Chemistry, 2019Co-Authors: Angelika Broer, Jeff Holst, Farid Rahimi, Gregory Gauthier-coles, Michelle Van Geldermalsen, Dieter Dorsch, Ansgar Wegener, Stefan BroerAbstract:: The neutral amino acid transporter solute carrier family 1 member 5 (SLC1A5 or ASCT2) is overexpressed in many cancers. To identify its roles in tumors, we employed 143B osteosarcoma cells and HCC1806 triple-negative breast cancer cells with or without ASCT2 deletion. ASCT2ko 143B cells grew well in standard culture media, but ASCT2 was required for optimal growth at
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Disruption of Amino Acid Homeostasis by Novel ASCT2 Inhibitors Involves Multiple Targets
Frontiers in Pharmacology, 2018Co-Authors: Angelika Broer, Stephen J. Fairweather, Stefan BroerAbstract:The glutamine transporter ASCT2 (SLC1A5) is actively investigated as an oncological target, but the field lacks efficient ASCT2 inhibitors. A new group of ASCT2 inhibitors, 2-Amino-4-bis(aryloxybenzyl)aminobutanoic acids (AABA) were developed recently and shown to suppress tumor growth in preclinical in vivo models. To test its specificity, we deleted ASCT2 in two human cancer cell lines. Surprisingly, growth of parental and ASCT2-knockout cells was equally sensitive to AABA compounds. AABA compounds inhibited glutamine transport in cells lacking ASCT2, but not in parental cells. Deletion of ASCT2 and amino acid depletion induced expression of SNAT2 (SLC38A2), the activity of which was inhibited by AABA compounds. They also potently inhibited isoleucine uptake via LAT1 (SLC7A5), a transporter that is upregulated in cancer cells together with ASCT2. Inhibition of SNAT2 and LAT1 was confirmed by recombinant expression in Xenopus laevis oocytes. The reported reduction of tumor growth in pre-clinical models may be explained by a significant disruption of amino acid homeostasis.
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asct2 SLC1A5 deficient mice have normal b cell development proliferation and antibody production
Frontiers in Immunology, 2017Co-Authors: Etienne Maslefarquhar, Angelika Broer, Mehmet Yabas, Anselm Enders, Stefan BroerAbstract:SLC1A5 (solute carrier family 1, member 5) is a small neutral amino acid exchanger that is up-regulated in rapidly proliferating lymphocytes, but also in many primary human cancers. Furthermore, cancer cell lines have been shown to require SLC1A5 for their survival in vitro. One of SLC1A5’s primary substrates is the immunomodulatory amino acid glutamine, which plays an important role in multiple key processes, such as energy supply, macromolecular synthesis, nucleotide biosynthesis, redox homeostasis and resistance against oxidative stress. These processes are also essential to immune cells, including neutrophils, macrophages, B and T lymphocytes. We show here that mice with a stop codon in SLC1A5 have reduced glutamine uptake in activated lymphocytes and primary fibroblasts. B and T cell populations and maturation in resting mice were not affected by absence of SLC1A5. Antibody production in resting and immunised mice and the germinal centre response to immunisation were also found to be normal. SLC1A5 has been recently described as a novel target for the treatment of a variety of cancers and our results indicate that inhibition of SLC1A5 in cancer therapy may be tolerated well by the immune system of cancer patients.
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deletion of amino acid transporter asct2 SLC1A5 reveals an essential role for transporters snat1 slc38a1 and snat2 slc38a2 to sustain glutaminolysis in cancer cells
Journal of Biological Chemistry, 2016Co-Authors: Angelika Broer, Farid Rahimi, Stefan BroerAbstract:Abstract Many cancer cells depend on glutamine as they use the glutaminolysis pathway to generate building blocks and energy for anabolic purposes. As a result, glutamine transporters are essential for cancer growth and are potential targets for cancer chemotherapy, with ASCT2 (SLC1A5) being investigated most intensively. Here we show that HeLa epithelial cervical cancer cells and 143B osteosarcoma cells express a set of glutamine transporters including SNAT1 (SLC38A1), SNAT2 (SLC38A2), SNAT4 (SLC38A4), LAT1 (SLC7A5), and ASCT2 (SLC1A5). Net glutamine uptake did not depend on ASCT2, but required expression of SNAT1 and SNAT2. Deletion of ASCT2, did not reduce cell growth but caused an amino acid starvation response and up-regulation of SNAT1 to replace ASCT2 functionally. Silencing of GCN2 in the ASCT2 (-/-) background reduced cell growth, showing that a combined targeted approach would inhibit growth of glutamine-dependent cancer cells.
Chun Lu - One of the best experts on this subject based on the ideXlab platform.
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effects of targeting SLC1A5 on inhibiting gastric cancer growth and tumor development in vitro and in vivo
Oncotarget, 2017Co-Authors: Jian Lu, Yang Li, Min Chen, Chun LuAbstract:// Jian Lu 1, 2, 3, * , Min Chen 1, 3, * , Zhenhua Tao 2 , Sumeng Gao 3 , Yang Li 1 , Yu Cao 1 , Chun Lu 4 and Xiaoping Zou 1, 3 1 Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008, P.R. China 2 Department of Gastroenterology, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi 214002, P.R. China 3 Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing 210008, P.R. China 4 Department of Microbiology, Nanjing Medical University, Nanjing 211116, P.R. China * These authors have contributed equally to this work Correspondence to: Chun Lu, email: clu@njmu.edu.cn Xiaoping Zou, email: 13770771661@163.com Keywords: SLC1A5, gastric cancer, cell proliferation, cell motility Received: April 15, 2017 Accepted: June 10, 2017 Published: July 22, 2017 ABSTRACT Aims: To investigate the oncogenic effects of SLC1A5 on gastric cancer development in vitro and in vivo . Methods: The expression level of SLC1A5 was detected in 70 gastric cancer paraffin-embedded tissues by immunohistochemistry and also was detected in gastric cancer cell lines by qRT-PCR and western blotting analysis. The effects of knockdown SLC1A5 were analyzed on cell proliferation, cell cycle, the ability of cell migration and invasion and growth signaling pathway in vitro . By using subcutaneous xenograft mouse, the importance of SLC1A5 expression was assessed for both successful engraftment and growth of gastric cancer cells in vivo . Results: SLC1A5 was up-regulated in gastric cancer tissues and was correlated with malignant features such as deeper local invasion, higher lymph node metastasis, advanced TNM stages and higher Ki-67 expression. Knockdown SLC1A5 in gastric cancer cells suppressed cell proliferation, caused G0/G1 arrest and inhibited cell invasion as well as migration partly by inactivated mTOR/p-70S6K1 signaling pathway in vitro . Furthermore, in vivo experiments indicated that suppression of SLC1A5 could inhibit relative volume of xenografted tumor. Conclusions: Our results suggested that SLC1A5 might be considered as a new biomarker and also as a potential therapeutic target in gastric cancer.
Mohamed Hassanein - One of the best experts on this subject based on the ideXlab platform.
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targeting SLC1A5 mediated glutamine dependence in non small cell lung cancer
International Journal of Cancer, 2015Co-Authors: Mohamed Hassanein, Xiangming Ji, Jun Qian, Megan Hoeksema, Bradford K Harris, Jing Wang, Marie Jacobovitz, Fredrick T Harris, Kelli L BoydAbstract:New therapeutic strategies are desperately needed in lung cancer. Targeting cancer-specific biochemical phenotypes, including those determined metabolically, represents an alternative approach to treating patients with lung cancer, the leading cause of cancer deaths in the USA and worldwide.1 L-Glutamine (Gln) is an essential amino acid for non-small cell lung cancer (NSCLC) growth in vitro and in vivo.2–4 Gln has been shown to sustain tumor growth under hypoxia,5 to mediate K-RAS-driven lung cancer growth6 and to support the autophagy-mediated prosurvival pathway in B-RAFV600-driven lung tumors.7 Nonetheless, the specific contribution of Gln transporters to lung cancer remains largely unknown. What’s new? New strategies to overcome lung cancer mortality depend heavily on the discovery of novel therapeutic targets. In non-small cell lung cancer (NSCLC), a possible target is solute linked carrier family 1A, member 5 (SLC1A5), a major glutamine transporter in NSCLC. This study furthers the promise of SLC1A5 by showing that its expression levels in lung cancer cells can predict cell sensitivity to the inhibitor gamma-L-glutamyl-p-nitroanilide (GPNA). In NSCLC cell lines, SLC1A5 inactivation led to glutamine starvation and oxidative stress-mediated autophagy and apoptosis. In NSCLC patients, SLC1A5 expression was associated with poor overall survival. We recently identified by in-depth shotgun proteomic analysis of stage I NSCLCs several therapeutic targets including the solute linked carrier family 1A, member 5 (SLC1A5).8 We were the first to report that SLC1A5 functions as the primary transporter of Gln in a sodium-dependent manner in NSCLC.9 Inhibition of SLC1A5 attenuates cell growth and mTOR signaling.9,10 Although pharmacological strategies to inhibit Gln metabolism using amino acid analogs such as acivicin and 6-diazo-5-oxo-L-norleucine (DON) have been investigated,3,11 the lack of selectivity of these agents has shifted the efforts to developing agents directed at specific nodes of glutamine metabolism instead.12 Given the emerging role of Gln metabolism in cancer13 and the differential expression of SLC1A5 in NSCLC,9 we tested the hypothesis that elevated SLC1A5 expression is a key prosurvival mechanism that promotes NSCLC progression by increasing tumor cells to transport and utilize Gln available in the microenvironment. We investigated the prognostic value of SLC1A5 expression in NSCLC and examined the therapeutic potential of targeting its Gln transport activity in cell and xenografts by inhibiting SLC1A5-dependent Gln transport.
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Abstract 1185: Regulation of neutral amino acid transporters gene expression profile in non-small cell lung cancer
Cancer Research, 2015Co-Authors: Pierre P. Massion, Maria Senosain, Mohamed Hassanein, Xiangming Ji, Jun Qian, Megan HoeksemaAbstract:Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA INTRODUCTION: In a recent study, we showed that SLC1A5, a key glutamine (Gln) transporter, regulates tumor growth and survival in NSCLC. Here we sought to characterize the expression of other Gln transporters in lung cancer and to test whether the inhibition of SLC1A5 activity induced a change in expression of other amino acid transporters in NSCLC. METHODS: Neutral amino acid transporters reported in the cancer literature were evaluated in publically available lung cancer gene expression datasets. Among those, SLC38A1, SLC1A4, SLC1A5, SLC7A5, SLC7A11, SLC7A8 were selected for the in vitro validation. The expression of these genes was evaluated in two lung squamous carcinoma cell lines (HCC15, H226) and one adenocarcinoma cell line (A549) by RT-PCR and then quantified by qPCR, using SYBR® Green Supermix protocol. The expression of the same genes was assessed in response to transient SLC1A5 knockdown in HCC15 and A549 cell lines by qPCR. RESULTS: Amino acid transporters SLC38A1, SLC1A5, SLC7A5 and SLC7A11 are expressed in NSCLCs, a finding that was confirmed in the three cell lines studied. SLC1A4 was found to have the lowest expression and SLC7A8 no expression in any of cell lines. In response to SLC1A5 transient knockdown in A549, SLC38A1, SLC1A4 and SLC7A5 were significantly up-regulated (p
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abstract b161 SLC1A5 inactivation induces apoptosis mediated cells death in non small cell lung cancer
Molecular Cancer Therapeutics, 2013Co-Authors: Mohamed Hassanein, Jun Qian, Megan Hoeksema, Bradford K Harris, Marie Jacobovitz, Fredrick T Harris, Pierre P. MassionAbstract:Introduction: We recently reported that solute carrier family A1 member 5 (SLC1A5) controls glutamine (GLN) uptake and modulates cell growth, oxidative stress and mTOR signalling pathway. SLC1A5 is a transmembrane, high affinity glutamine transporter that is overexpressed and located at the plasma membrane in non-small cell lung cancer (NSCLC). GLN deprivation has been shown to induce cell death in several types of cancers, however the exact mechanism by which SLC1A5 targeting affects NSCLC survival remains unknown. We hypothesize that inhibition of SLC1A5 deprives cells from GLN which induces autophagy which eventually leads to cell starvation and ultimately apoptotic cell death. Methods: To test our hypothesis we targeted SLC1A5 by siRNA or by its specific inhibitor, GPNA, in a panel of 6 NSCLC lung cancer cell lines (express high level of SLC1A5). For comparison 2 human bronchial epithelial cell lines (HBEs) (express low level of SLC1A5) were used. The effects of targeting SLC1A5 on growth, GLN uptake, ATP level, autophagy, and cell death were examined. Markers of autophagy and cell death were analysed using western blot, nuclear staining and cell cycle analysis. Results: SLC1A5 inactivation by GPNA or by siRNA resulted in a significant decrease in cellular GLN uptake in NSCLC cell lines, while HBE cell lines were unaffected. Decrease in GLN uptake was accompanied by an increase in autophagy as evident by decrease in cell size, increase of LC3-II and decrease if LC3-I markers of autophagy. In addition, we observed a significant drop in ATP levels by 2 folds with increasing doses of GPNA. Markers of internal apoptotic pathway that include decrease of mitochondrial potential and cleaved caspases-3 and 9 were detected in response to increasing doses of GPNA. No change was observed in external apoptotic markers, caspases 8 or 1. In addition a 2-10 fold increase (based on the cell line) of sub-G1 was observed in NSCLC cell lines but not in HBE cell lines. Conclusion: Our results show that targeting SLC1A5 in NSCLC cells induces apoptotic cell death. Cells starve due to GLN deprivation and undergo autophagy which leads to a decrease in ATP level resulting in apoptotic cell death. These findings suggest that targeting SLC1A5 may have therapeutic implications in NSCLC. Grant funding: Lung Cancer Research Foundation Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B161. Citation Format: Mohamed Hassanein, Jun Qian, Megan Hoeksema, Marie Jacobovitz, Fredrick T. Harris, Bradford Harris, Pierre P. Massion. SLC1A5 inactivation induces apoptosis-mediated cells death in non-small cell lung cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B161.
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SLC1A5 mediates glutamine transport required for lung cancer cell growth and survival
Clinical Cancer Research, 2013Co-Authors: Mohamed Hassanein, Jun Qian, Masakazu Shiota, Bradford K Harris, Heidi Chen, Jonathan E Clark, William E Alborn, Rosana Eisenberg, Pierre P. MassionAbstract:Purpose: We have previously identified solute-linked carrier family A1 member 5 (SLC1A5) as an overexpressed protein in a shotgun proteomic analysis of stage I non–small cell lung cancer (NSCLC) when compared with matched controls. We hypothesized that overexpression of SLC1A5 occurs to meet the metabolic demand for lung cancer cell growth and survival. Experimental Design: To test our hypothesis, we first analyzed the protein expression of SLC1A5 in archival lung cancer tissues by immunohistochemistry and immunoblotting ( N = 98) and in cell lines ( N = 36). To examine SLC1A5 involvement in amino acid transportation, we conducted kinetic analysis of l-glutamine (Gln) uptake in lung cancer cell lines in the presence and absence of a pharmacologic inhibitor of SLC1A5, gamma-l-Glutamyl-p-Nitroanilide (GPNA). Finally, we examined the effect of Gln deprivation and uptake inhibition on cell growth, cell-cycle progression, and growth signaling pathways of five lung cancer cell lines. Results: Our results show that (i) SLC1A5 protein is expressed in 95% of squamous cell carcinomas (SCC), 74% of adenocarcinomas (ADC), and 50% of neuroendocrine tumors; (ii) SLC1A5 is located at the cytoplasmic membrane and is significantly associated with SCC histology and male gender; (iii) 68% of Gln is transported in a Na + -dependent manner, 50% of which is attributed to SLC1A5 activity; and (iv) pharmacologic and genetic targeting of SLC1A5 decreased cell growth and viability in lung cancer cells, an effect mediated in part by mTOR signaling. Conclusions: These results suggest that SLC1A5 plays a key role in Gln transport controlling lung cancer cells9 metabolism, growth, and survival. Clin Cancer Res; 19(3); 560–70. ©2012 AACR .
Jiejie Xu - One of the best experts on this subject based on the ideXlab platform.
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high expression of solute carrier family 1 member 5 SLC1A5 is associated with poor prognosis in clear cell renal cell carcinoma
Scientific Reports, 2015Co-Authors: Liu Yang, Huimin An, Yuan Chang, Weijuan Zhang, Le Xu, Jiejie XuAbstract:Solute Carrier Family 1, member 5 (SLC1A5), also named as ASCT2, a major glutamine transporter, is highly expressed in various malignancies and plays a critical role in the transformation, growth and survival of cancer cells. The aim of this study was to assess the clinical significance of SLC1A5 in patients with clear-cell renal cell carcinoma (ccRCC). SLC1A5 expression was evaluated by immunohistochemistry on tissue microarrays. Kaplan-Meier method was conducted to compare survival curves. Univariate and multivariate Cox regression models were applied to assess the impact of prognostic factors on overall survival (OS). A nomogram was then constructed on the basis of the independent prognosticators identified on multivariate analysis. The predictive ability of the models was compared using Receiver operating characteristic (ROC) analysis. Our data indicated that high expression of SLC1A5 was significantly associated with advanced TNM stage, higher Fuhrman grade and shorter OS in ccRCC patients. Multivariate analysis confirmed that SLC1A5 was an independent prognosticator for OS. A nomogram integrating SLC1A5 and other independent prognosticators was constructed, which showed a better prognostic value for OS than TNM staging system. In conclusion, high SLC1A5 expression is an independent predictor of adverse clinical outcome in ccRCC patients after surgery.
Fredrick T Harris - One of the best experts on this subject based on the ideXlab platform.
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targeting SLC1A5 mediated glutamine dependence in non small cell lung cancer
International Journal of Cancer, 2015Co-Authors: Mohamed Hassanein, Xiangming Ji, Jun Qian, Megan Hoeksema, Bradford K Harris, Jing Wang, Marie Jacobovitz, Fredrick T Harris, Kelli L BoydAbstract:New therapeutic strategies are desperately needed in lung cancer. Targeting cancer-specific biochemical phenotypes, including those determined metabolically, represents an alternative approach to treating patients with lung cancer, the leading cause of cancer deaths in the USA and worldwide.1 L-Glutamine (Gln) is an essential amino acid for non-small cell lung cancer (NSCLC) growth in vitro and in vivo.2–4 Gln has been shown to sustain tumor growth under hypoxia,5 to mediate K-RAS-driven lung cancer growth6 and to support the autophagy-mediated prosurvival pathway in B-RAFV600-driven lung tumors.7 Nonetheless, the specific contribution of Gln transporters to lung cancer remains largely unknown. What’s new? New strategies to overcome lung cancer mortality depend heavily on the discovery of novel therapeutic targets. In non-small cell lung cancer (NSCLC), a possible target is solute linked carrier family 1A, member 5 (SLC1A5), a major glutamine transporter in NSCLC. This study furthers the promise of SLC1A5 by showing that its expression levels in lung cancer cells can predict cell sensitivity to the inhibitor gamma-L-glutamyl-p-nitroanilide (GPNA). In NSCLC cell lines, SLC1A5 inactivation led to glutamine starvation and oxidative stress-mediated autophagy and apoptosis. In NSCLC patients, SLC1A5 expression was associated with poor overall survival. We recently identified by in-depth shotgun proteomic analysis of stage I NSCLCs several therapeutic targets including the solute linked carrier family 1A, member 5 (SLC1A5).8 We were the first to report that SLC1A5 functions as the primary transporter of Gln in a sodium-dependent manner in NSCLC.9 Inhibition of SLC1A5 attenuates cell growth and mTOR signaling.9,10 Although pharmacological strategies to inhibit Gln metabolism using amino acid analogs such as acivicin and 6-diazo-5-oxo-L-norleucine (DON) have been investigated,3,11 the lack of selectivity of these agents has shifted the efforts to developing agents directed at specific nodes of glutamine metabolism instead.12 Given the emerging role of Gln metabolism in cancer13 and the differential expression of SLC1A5 in NSCLC,9 we tested the hypothesis that elevated SLC1A5 expression is a key prosurvival mechanism that promotes NSCLC progression by increasing tumor cells to transport and utilize Gln available in the microenvironment. We investigated the prognostic value of SLC1A5 expression in NSCLC and examined the therapeutic potential of targeting its Gln transport activity in cell and xenografts by inhibiting SLC1A5-dependent Gln transport.
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abstract b161 SLC1A5 inactivation induces apoptosis mediated cells death in non small cell lung cancer
Molecular Cancer Therapeutics, 2013Co-Authors: Mohamed Hassanein, Jun Qian, Megan Hoeksema, Bradford K Harris, Marie Jacobovitz, Fredrick T Harris, Pierre P. MassionAbstract:Introduction: We recently reported that solute carrier family A1 member 5 (SLC1A5) controls glutamine (GLN) uptake and modulates cell growth, oxidative stress and mTOR signalling pathway. SLC1A5 is a transmembrane, high affinity glutamine transporter that is overexpressed and located at the plasma membrane in non-small cell lung cancer (NSCLC). GLN deprivation has been shown to induce cell death in several types of cancers, however the exact mechanism by which SLC1A5 targeting affects NSCLC survival remains unknown. We hypothesize that inhibition of SLC1A5 deprives cells from GLN which induces autophagy which eventually leads to cell starvation and ultimately apoptotic cell death. Methods: To test our hypothesis we targeted SLC1A5 by siRNA or by its specific inhibitor, GPNA, in a panel of 6 NSCLC lung cancer cell lines (express high level of SLC1A5). For comparison 2 human bronchial epithelial cell lines (HBEs) (express low level of SLC1A5) were used. The effects of targeting SLC1A5 on growth, GLN uptake, ATP level, autophagy, and cell death were examined. Markers of autophagy and cell death were analysed using western blot, nuclear staining and cell cycle analysis. Results: SLC1A5 inactivation by GPNA or by siRNA resulted in a significant decrease in cellular GLN uptake in NSCLC cell lines, while HBE cell lines were unaffected. Decrease in GLN uptake was accompanied by an increase in autophagy as evident by decrease in cell size, increase of LC3-II and decrease if LC3-I markers of autophagy. In addition, we observed a significant drop in ATP levels by 2 folds with increasing doses of GPNA. Markers of internal apoptotic pathway that include decrease of mitochondrial potential and cleaved caspases-3 and 9 were detected in response to increasing doses of GPNA. No change was observed in external apoptotic markers, caspases 8 or 1. In addition a 2-10 fold increase (based on the cell line) of sub-G1 was observed in NSCLC cell lines but not in HBE cell lines. Conclusion: Our results show that targeting SLC1A5 in NSCLC cells induces apoptotic cell death. Cells starve due to GLN deprivation and undergo autophagy which leads to a decrease in ATP level resulting in apoptotic cell death. These findings suggest that targeting SLC1A5 may have therapeutic implications in NSCLC. Grant funding: Lung Cancer Research Foundation Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B161. Citation Format: Mohamed Hassanein, Jun Qian, Megan Hoeksema, Marie Jacobovitz, Fredrick T. Harris, Bradford Harris, Pierre P. Massion. SLC1A5 inactivation induces apoptosis-mediated cells death in non-small cell lung cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B161.