The Experts below are selected from a list of 1410 Experts worldwide ranked by ideXlab platform

Linheng Li - One of the best experts on this subject based on the ideXlab platform.

Ruilian Xu - One of the best experts on this subject based on the ideXlab platform.

Thomas Gridley - One of the best experts on this subject based on the ideXlab platform.

  • BMPs and FGFs target Notch signalling via jagged 2 to regulate tooth morphogenesis and cytodifferentiation
    Development, 2010
    Co-Authors: Thimios A. Mitsiadis, Thomas Gridley, Daniel Graf, Hansueli Luder, Gilles Bluteau
    Abstract:

    The Notch signalling pathway is an evolutionarily conserved intercellular signalling mechanism that is essential for cell fate specification and proper embryonic development. We have analysed the expression, regulation and function of the jagged 2 (JAG2) gene, which encodes a ligand for the Notch family of receptors, in developing mouse teeth. JAG2 is expressed in epithelial cells that give rise to the enamel-producing ameloblasts from the earliest stages of tooth development. Tissue recombination experiments showed that its expression in epithelium is regulated by mesenchyme-derived signals. In dental explants cultured in vitro, the local application of fibroblast growth factors upregulated JAG2 expression, whereas bone morphogenetic proteins provoked the opposite effect. Mice homozygous for a deletion in the Notch-interaction domain of JAG2 presented a variety of severe dental abnormalities. In molars, the crown morphology was misshapen, with additional cusps being formed. This was due to alterations in the enamel knot, an epithelial signalling structure involved in molar crown morphogenesis, in which Bmp4 expression and apoptosis were altered. In incisors, cytodifferentiation and enamel matrix deposition were inhibited. The expression of Tbx1 in ameloblast progenitors, which is a hallmark for ameloblast differentiation and enamel formation, was dramatically reduced in JAG2−/− teeth. Together, these results demonstrate that Notch signalling mediated by JAG2 is indispensable for normal tooth development.

  • Generation of mice with a conditional null allele of the Jagged2 gene
    Genesis, 2010
    Co-Authors: Jingxia Xu, Luke T. Krebs, Thomas Gridley
    Abstract:

    The Notch signaling pathway is an evolutionarily conserved intercellular signaling mechanism. Mutations in Notch pathway components disrupt embryonic development in diverse multicellular organisms and cause cancers and inherited disease syndromes in humans (Bray, 2006; Fiuza and Arias, 2007). In mammals, genes of the Notch family (Notch1 through Notch4) encode Type 1 transmembrane protein receptors that interact with Type 1 transmembrane ligands encoded by genes of the Delta-like (Dll1, Dll3 and Dll4) and Jagged (Jag1 and JAG2) families. We have previously described the construction and analysis of a targeted null allele of the Jagged2 (JAG2) gene, termed JAG2del1 (originally named JAG2ΔDSL) (Jiang et al., 1998). JAG2del1/JAG2del1 homozygous mutant mice die at birth from completely penetrant cleft palate. The JAG2del1/JAG2del1 mice also exhibit soft tissue syndactyly, the fusion of the digits on the fore- and hindlimbs (Jiang et al., 1998). Cleft palate and soft tissue syndactyly are also exhibited at reduced penetrance by mice homozygous for the syndactylism mutation, a spontaneous JAG2 missense mutant allele (JAG2sm) that behaves genetically as a JAG2 hypomorphic allele (Casey et al., 2006; Sidow et al., 1997). To circumvent the neonatal lethality exhibited by JAG2del1/JAG2del1 null mutant mice and permit the study of JAG2 function in postnatal and adult mice, we describe here construction of an allele for conditional inactivation of JAG2 gene function using the Cre-loxP system. The JAG2 gene spans approximately 21 kb on mouse Chromosome 12, and consists of 26 exons. To generate the JAG2floxneo targeting vector (Fig. 1a), a PGKneo selection cassette was introduced into intron 2. The PGKneo cassette was flanked by FRT sites for removal by Flpe recombinase (Farley et al., 2000), and by a loxP site distal to the PGKneo cassette in intron 2. A second loxP site was introduced approximately 1.1 kb upstream of the JAG2 translational start site. A diphtheria toxin cassette, at the terminus of the targeting vector, was introduced for negative selection against random integration of the targeting vector into the ES cell genome. The design of the JAG2floxneo allele permits removal of the PGKneo cassette by mating to a Flpe deleter mouse line (generating the JAG2flox allele), or removal of JAG2 genomic sequence (including promoter sequences and exons 1 and 2) and the PGKneo cassette by mating to a Cre deleter line. To distinguish the JAG2 mutant allele generated by Cre-mediated deletion of the JAG2flox or JAG2floxneo alleles from the JAG2del1 allele, our previously published JAG2 targeted null mutant allele (Jiang et al., 1998), we designate the JAG2 null allele generated by Cre recombinase-mediated deletion of the JAG2flox or JAG2floxneo alleles the JAG2del2 allele. FIG. 1 Generation of a JAG2 conditional null allele. (a) Schematic representation of a portion of the wildtype JAG2 allele, the JAG2floxneo targeting vector, and the targeted JAG2floxneo allele. Exons are indicated by boxes with coding sequences designated by ... The JAG2floxneo targeting construct was electroporated into R1 ES cells (Nagy et al., 1993), and three correctly targeted clones (Fig. 1b) were injected into C57BL/6J blastocysts. Chimeras were mated to C57BL/6J female mice, and germline transmission was obtained from one clone. JAG2floxneo/+ heterozygous mice were mated to a deleter line expressing the Flpe recombinase (Farley et al., 2000) to excise the PGKneo cassette and generate the JAG2flox allele. Mice heterozygous for the JAG2del2 null allele were generated by mating JAG2flox/+ heterozygous mice to Meox2-Cre mice which, in addition to other tissues, express Cre recombinase in the germline (Tallquist and Soriano, 2000). As with the JAG2del1 allele, heterozygous JAG2del2/+ mice were viable, fertile and displayed no obvious phenotypic abnormalities. Cre-mediated excision of the JAG2flox allele to generate the JAG2del2 allele deletes predicted JAG2 promoter sequences, the ATG translation start site and exons 1 and 2, which we predict would create a JAG2 null allele. In order to assess the functionality of the JAG2del2 allele, embryos and neonatal mice homozygous for the JAG2del2 allele were obtained by intercrossing JAG2del2/+ heterozygous mice. We assessed JAG2 RNA expression in JAG2del2/JAG2del2 and JAG2del2/+ littermate control embryos at E10.5 by whole mount in situ hybridization. JAG2 RNA was not expressed at levels detectable by in situ hybridization in JAG2del2/JAG2del2 homozygous mutant embryos (Fig. 2). We also assessed JAG2 RNA expression in homozygous JAG2del2/JAG2del2 mice by quantitative RT-PCR. Using a primer set that spanned exons 3 and 4, JAG2del2/JAG2del2 homozygous mutants expressed 11.5 ± 1.3% of wildtype JAG2 transcript levels. Utilizing a primer set spanning exons 6–8 of the JAG2 gene, JAG2del2/JAG2del2 mutant embryos expressed 21.8± 3.6% of wildtype JAG2 transcript levels. However, these levels of the JAG2del2 mutant transcript do not appear to have any functional consequences, since JAG2del2/JAG2del2 homozygous mutant mice exhibited a phenotype identical to that exhibited by JAG2del1/JAG2del1 null mutant mice (Fig. 3). JAG2del2/JAG2del2 neonates died the first day of birth, exhibiting syndactyly of the fore- and hindlimbs and palate-tongue fusions that caused palatal clefting (Fig. 3). These data demonstrate that the JAG2del2 allele is a JAG2 null allele, functionally equivalent to the JAG2del1 allele, and that the extent of Cre-mediated deletion of the JAG2flox allele can be assessed by in situ hybridization. The neonatal lethality of JAG2 null mice has precluded analysis of JAG2 function in postnatal and adult mice. Utilization of the JAG2flox conditional null allele will enable the investigation of JAG2 function in a tissue-specific manner throughout the mouse life span. FIG. 2 Absence of JAG2 RNA expression in JAG2del2/JAG2del2 embryos. (a,b) Whole mount in situ hybridization for JAG2 transcripts in JAG2del2/+ control littermate (a,c,e,g) and JAG2del2/JAG2del2 (b,d,f,h) embryos at E10.5. JAG2 RNA was not detectable by in situ ... FIG. 3 Phenotype of JAG2del2 homozygous mutant embryos. (a–c) Cleft palate in JAG2del2/JAG2del2 homozygotes. Coronal sections of E16.5 embryos show that the JAG2del2/JAG2del2 homozygote has cleft palate and fused tongue. (c) Fusion of the tongue with ...

  • JAG2 notch1 signaling regulates oral epithelial differentiation and palate development
    Developmental Dynamics, 2006
    Co-Authors: Liam M Casey, Thomas Gridley, Kathleen M Maltby, Rulang Jiang
    Abstract:

    During mammalian palatogenesis, palatal shelves initially grow vertically from the medial sides of the paired maxillary processes flanking the developing tongue and subsequently elevate and fuse with each other above the tongue to form the intact secondary palate. Pathological palate–mandible or palate–tongue fusions have been reported in humans and other mammals, but the molecular and cellular mechanisms that prevent such aberrant adhesions during normal palate development are unknown. We previously reported that mice deficient in JAG2, which encodes a cell surface ligand for the Notch family receptors, have cleft palate associated with palate–tongue fusions. In this report, we show that JAG2 is expressed throughout the oral epithelium and is required for Notch1 activation during oral epithelial differentiation. We show that Notch1 is normally highly activated in the differentiating oral periderm cells covering the developing tongue and the lateral oral surfaces of the mandibular and maxillary processes during palate development. Oral periderm activation of Notch1 is significantly attenuated during palate development in the JAG2 mutants. Further molecular and ultrastructural analyses indicate that oral epithelial organization and periderm differentiation are disrupted in the JAG2 mutants. Moreover, we show that the JAG2 mutant tongue fused to wild-type palatal shelves in recombinant explant cultures. These data indicate that JAG2-Notch1 signaling is spatiotemporally regulated in the oral epithelia during palate development to prevent premature palatal shelf adhesion to other oral tissues and to facilitate normal adhesion between the elevated palatal shelves. Developmental Dynamics 235:1830–1844, 2006. © 2006 Wiley-Liss, Inc.

  • the notch ligands dll1 and JAG2 act synergistically to regulate hair cell development in the mammalian inner ear
    Development, 2005
    Co-Authors: Amy E Kiernan, Ralf Cordes, Raphael Kopan, Achim Gossler, Thomas Gridley
    Abstract:

    The mammalian auditory sensory epithelium, the organ of Corti, contains sensory hair cells and nonsensory supporting cells arranged in a highly patterned mosaic. Notch-mediated lateral inhibition is the proposed mechanism for creating this sensory mosaic. Previous work has shown that mice lacking the Notch ligand JAG2 differentiate supernumerary hair cells in the cochlea, consistent with the lateral inhibitory model. However, it was not clear why only relatively modest increases in hair cell production were observed in JAG2 mutant mice. Here, we show that another Notch ligand, DLL1, functions synergistically with JAG2 in regulating hair cell differentiation in the cochlea. We also show by conditional inactivation that these ligands probably signal through the NOTCH1 receptor. Supernumerary hair cells in Dll1/JAG2 double mutants arise primarily through a switch in cell fate, rather than through excess proliferation. Although these results demonstrate an important role for Notch-mediated lateral inhibition during cochlear hair cell patterning, we also detected abnormally prolonged cellular proliferation that preferentially affected supporting cells in the organ of Corti. Our results demonstrate that the Notch pathway plays a dual role in regulating cellular differentiation and patterning in the cochlea, acting both through lateral inhibition and the control of cellular proliferation.

  • A mutation in the Lunatic fringe gene suppresses the effects of a Jagged2 mutation on inner hair cell development in the cochlea
    Current Biology, 2000
    Co-Authors: Nian Zhang, Gregory V. Martin, Matthew W. Kelley, Thomas Gridley
    Abstract:

    Abstract Recent studies have demonstrated that the Notch signaling pathway regulates the differentiation of sensory hair cells in the vertebrate inner ear [1–9]. We have shown previously that in mice homozygous for a targeted null mutation of the Jagged2 ( JAG2 ) gene, which encodes a Notch ligand, supernumerary hair cells differentiate in the cochlea of the inner ear [7]. Other components of the Notch pathway, including the Lunatic fringe ( Lfng ) gene, are also expressed during differentiation of the inner ear in mice [6–10]. In contrast to the JAG2 gene, which is expressed in hair cells, the Lfng gene is expressed in non-sensory supporting cells in the mouse cochlea [10]. Here we demonstrate that a mutation in the Lfng gene partially suppresses the effects of the JAG2 mutation on hair cell development. In mice homozygous for targeted mutations of both JAG2 and Lfng , the generation of supernumerary hair cells in the inner hair cell row is suppressed, while supernumerary hair cells in the outer hair cell rows are unaffected. We also demonstrate that supernumerary hair cells are generated in mice heterozygous for a Notch1 mutation. We suggest a model for the action of the Notch signaling pathway in regulating hair cell differentiation in the cochlear sensory epithelium.

Hongbing Zhang - One of the best experts on this subject based on the ideXlab platform.

  • abstract 3551 a microrna 1280 JAG2 network comprises a novel biological target in high risk medulloblastoma
    Cancer Research, 2015
    Co-Authors: Fengfei Wang, Marc Remke, Kruttika Bhat, Eric T Wong, Shuang Zhou, Vijay Ramaswamy, Adrian M Dubuc, Ekokobe Fonkem, Saeed Salem, Hongbing Zhang
    Abstract:

    Over-expression of PDGF receptors (PDGFRs) has been previously implicated in high-risk medulloblastoma (MB) pathogenesis. However, the exact biological functions of PDGFRα and PDGFRβ signaling in MB biology remain poorly understood. Here, we report the subgroup specific expression of PDGFRα and PDGFRβ and their associated biological pathways in MB tumors. c-MYC, a downstream target of PDGFRβ but not PDGFRα, is involved in PDGFRβ signaling associated with cell proliferation, cell death, and invasion. Concurrent inhibition of PDGFRβ and c-MYC blocks MB cell proliferation and migration synergistically. Integrated analysis of miRNA and miRNA targets regulated by both PDGFRβ and c-MYC reveals that increased expression of JAG2, a target of miR-1280, is associated with high metastatic dissemination at diagnosis and a poor outcome in MB patients. Our study may resolve the controversy on the role of PDGFRs in MB and unveils JAG2 as a key downstream effector of a PDGFRβ-driven signaling cascade and a potential therapeutic target. Citation Format: Fengfei Wang, Marc Remke, Kruttika Bhat, Eric Wong, Shuang Zhou, Vijay Ramaswamy, Adrian Dubuc, Ekokobe Fonkem, Saeed Salem, Hongbing Zhang, Tze-chen Hsieh, Stephen O9Rourke, Lizi Wu, David Li, Cynthia Hawkins, Isaac Kohane, Joseph Wu, Min Wu, Michael Taylor, Erxi Wu. A microRNA-1280/JAG2 network comprises a novel biological target in high-risk medulloblastoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3551. doi:10.1158/1538-7445.AM2015-3551

  • Abstract 3551: A microRNA-1280/JAG2 network comprises a novel biological target in high-risk medulloblastoma
    Cancer Research, 2015
    Co-Authors: Fengfei Wang, Marc Remke, Kruttika Bhat, Eric T Wong, Shuang Zhou, Vijay Ramaswamy, Adrian M Dubuc, Ekokobe Fonkem, Saeed Salem, Hongbing Zhang
    Abstract:

    Over-expression of PDGF receptors (PDGFRs) has been previously implicated in high-risk medulloblastoma (MB) pathogenesis. However, the exact biological functions of PDGFRα and PDGFRβ signaling in MB biology remain poorly understood. Here, we report the subgroup specific expression of PDGFRα and PDGFRβ and their associated biological pathways in MB tumors. c-MYC, a downstream target of PDGFRβ but not PDGFRα, is involved in PDGFRβ signaling associated with cell proliferation, cell death, and invasion. Concurrent inhibition of PDGFRβ and c-MYC blocks MB cell proliferation and migration synergistically. Integrated analysis of miRNA and miRNA targets regulated by both PDGFRβ and c-MYC reveals that increased expression of JAG2, a target of miR-1280, is associated with high metastatic dissemination at diagnosis and a poor outcome in MB patients. Our study may resolve the controversy on the role of PDGFRs in MB and unveils JAG2 as a key downstream effector of a PDGFRβ-driven signaling cascade and a potential therapeutic target. Citation Format: Fengfei Wang, Marc Remke, Kruttika Bhat, Eric Wong, Shuang Zhou, Vijay Ramaswamy, Adrian Dubuc, Ekokobe Fonkem, Saeed Salem, Hongbing Zhang, Tze-chen Hsieh, Stephen O9Rourke, Lizi Wu, David Li, Cynthia Hawkins, Isaac Kohane, Joseph Wu, Min Wu, Michael Taylor, Erxi Wu. A microRNA-1280/JAG2 network comprises a novel biological target in high-risk medulloblastoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3551. doi:10.1158/1538-7445.AM2015-3551

  • a microrna 1280 JAG2 network comprises a novel biological target in high risk medulloblastoma
    Oncotarget, 2015
    Co-Authors: Fengfei Wang, Marc Remke, Kruttika Bhat, Eric T Wong, Shuang Zhou, Vijay Ramaswamy, Adrian M Dubuc, Ekokobe Fonkem, Saeed Salem, Hongbing Zhang
    Abstract:

    Over-expression of PDGF receptors (PDGFRs) has been previously implicated in high-risk medulloblastoma (MB) pathogenesis. However, the exact biological functions of PDGFRα and PDGFRβ signaling in MB biology remain poorly understood. Here, we report the subgroup specific expression of PDGFRα and PDGFRβ and their associated biological pathways in MB tumors. c-MYC, a downstream target of PDGFRβ but not PDGFRα, is involved in PDGFRβ signaling associated with cell proliferation, cell death, and invasion. Concurrent inhibition of PDGFRβ and c-MYC blocks MB cell proliferation and migration synergistically. Integrated analysis of miRNA and miRNA targets regulated by both PDGFRβ and c-MYC reveals that increased expression of JAG2, a target of miR-1280, is associated with high metastatic dissemination at diagnosis and a poor outcome in MB patients. Our study may resolve the controversy on the role of PDGFRs in MB and unveils JAG2 as a key downstream effector of a PDGFRβ-driven signaling cascade and a potential therapeutic target.

  • A microRNA-1280/JAG2 network comprises a novel biological target in high-risk medulloblastoma
    Oncotarget, 2014
    Co-Authors: Fengfei Wang, Marc Remke, Kruttika Bhat, Eric T Wong, Shuang Zhou, Vijay Ramaswamy, Adrian M Dubuc, Ekokobe Fonkem, Saeed Salem, Hongbing Zhang
    Abstract:

    Over-expression of PDGF receptors (PDGFRs) has been previously implicated in high-risk medulloblastoma (MB) pathogenesis. However, the exact biological functions of PDGFRα and PDGFRβ signaling in MB biology remain poorly understood. Here, we report the subgroup specific expression of PDGFRα and PDGFRβ and their associated biological pathways in MB tumors. c-MYC, a downstream target of PDGFRβ but not PDGFRα, is involved in PDGFRβ signaling associated with cell proliferation, cell death, and invasion. Concurrent inhibition of PDGFRβ and c-MYC blocks MB cell proliferation and migration synergistically. Integrated analysis of miRNA and miRNA targets regulated by both PDGFRβ and c-MYC reveals that increased expression of JAG2, a target of miR-1280, is associated with high metastatic dissemination at diagnosis and a poor outcome in MB patients. Our study may resolve the controversy on the role of PDGFRs in MB and unveils JAG2 as a key downstream effector of a PDGFRβ-driven signaling cascade and a potential therapeutic target.

Wan He - One of the best experts on this subject based on the ideXlab platform.

  • mutual regulation of JAG2 and praf2 promotes migration and invasion of colorectal cancer cells uncoupled from epithelial mesenchymal transition
    Cancer Cell International, 2019
    Co-Authors: Wan He, Wenwen Li, Jun Tang, Yong Li, Lisheng He, Keli Zhong, Ruilian Xu
    Abstract:

    Background Our previous studies revealed that Jagged 2 (JAG2) is involved in the regulation of migration and invasion of colon cancer cells without affecting cell proliferation. This study further explored the specific mechanism by which JAG2 promotes migration and invasion of colorectal cancer cells.

  • effect of JAG2 on migration and invasion in colorectal cancer cell by praf2 independent of epithelial mesenchymal transition
    Journal of Clinical Oncology, 2019
    Co-Authors: Wan He, Han Wu, Wenwen Li, Ruilian Xu
    Abstract:

    e15107Background: Our previous studies revealed the increased expression of Jagged 2 (JAG2) in most intestinal cancer tissues. In colon cancer cell lines, JAG2 involved in the regulation of migrati...

  • Jagged 2 silencing inhibits motility and invasiveness of colorectal cancer cell lines
    Oncology Letters, 2016
    Co-Authors: Wan He, Charles Ming Lok Chan, Sze Chuen Cesar Wong, Thomas Chi Chuen Au, Shan Ho, Amanda Kit Ching Chan, Andrew Sai Kit Chan, Anthony T.c. Chan
    Abstract:

    Although the Notch pathway has been reported to be activated in colorectal cancer (CRC), limited information is available regarding the expression and role of its ligand, Jagged 2 (JAG2), in CRC. Using immunohistochemistry, the present study demonstrated that JAG2 protein expression may be detected in up to 95% of CRC cases and is 3-fold upregulated in tumor cells compared to surrounding normal tissues. This finding suggests that JAG2 may have a role in the tumorigenicity of CRC. To further investigate the cellular functions of JAG2 expression in CRC, two different small interfering RNAs (siRNAs) were used to downregulate JAG2 expression in CRC cell lines (HCT116, DLD-1 and HT-29). The results indicated that JAG2 knockdown inhibits the motility and invasiveness of CRC cell lines without significantly affecting cell proliferation. These findings implicate JAG2 in promoting aggressiveness of CRC, and lay the foundation for its future development as a therapeutic target for the treatment of CRC.

  • Abstract 505: Jagged 2 knockdown inhibits invasion in colorectal cancer cell lines
    Cancer Research, 2012
    Co-Authors: Wan He, Shan Ho, Sc Cesar Wong, Charles Ml Chan, Thomas Cc Au, Anthony T.c. Chan
    Abstract:

    Background: The notch pathway is involved in control of cell differentiation in various tissues including pancreas, muscle and bone marrow. Jagged 2 (JAG2) is a ligand for the notch pathway and was found to be overexpressed in malignant plasma cells from patients with multiple myeloma, causing the secretion and release of IL-6, VEGF, and IGF-1 in the microenvironment supporting myeloma cell growth. In breast cancers, it was found to be overexpressed at the hypoxic invasive front and was significantly correlated with metastasis free survival. Furthermore, up-regulation of JAG2 expression in mouse lung adenocarcinoma cells promoted its metastasis in mice. However, the expression pattern and function of JAG2 in colorectal cancer (CRC) is not clear. Therefore in this study, we examined the expression of JAG2 in CRC cell lines and determined the effect(s) of JAG2 knockdown by RNA interference in CRC cell lines. Materials and Methods: The expression of JAG2 protein was examined in four CRC cell lines (SW480, SW620, HCT116, DLD-1) and also in 1 normal colon epithelial cell line (CCD18co) using the western blot. To investigate the effects JAG2 knockdown in CRC cell lines, a pool of 4 siRNAs against JAG2 was transfected into the 4 CRC cell lines listed above. The effects on cell growth was then determined by the CellTiter 96® AQueous One Solution Cell Proliferation Assay (the MTS assay) and the Matrigel invasion assay was performed to assess its effects on invasive capability. Results: Western blot results showed that JAG2 protein was expressed in all 4 colorectal cancer cell lines including SW480, SW620, HCT116 and DLD-1 but not in the CCD18co normal colon epithelial cell line. The MTS assay showed that cell growth was not affected by JAG2 knockdown in the CRC cell lines. Interestingly, the invasive capability of HCT116 and DLD-1cells was reduced after JAG2 knockdown. Conclusions: Results from this study suggest that JAG2 may play a role in the invasiveness of CRC cell lines but not in cell proliferation. JAG2 may be a promising therapeutic target for inhibition of metastasis in colorectal cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 505. doi:1538-7445.AM2012-505