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dc.contributor.authorBlanchard, T.G.
dc.contributor.authorCzinn, S.J.
dc.contributor.authorBanerjee, V.
dc.date.accessioned2019-03-29T14:47:34Z
dc.date.available2019-03-29T14:47:34Z
dc.date.issued2019
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85062385902&doi=10.3390%2fcancers11020199&partnerID=40&md5=bcc441177fbc9e481feb6a975e9d9eaf
dc.identifier.urihttp://hdl.handle.net/10713/8656
dc.description.abstractMetastatic colorectal cancer (mCRC) is characterized by the expression of cellular oncogenes, the loss of tumor suppressor gene function. Therefore, identifying integrated signaling between onco-suppressor genes may facilitate the development of effective therapy for mCRC. To investigate these pathways we utilized cell lines and patient derived organoid models for analysis of gene/protein expression, gene silencing, overexpression, and immunohistochemical analyses. An inverse relationship in expression of oncogenic FoxM1 and tumor suppressor RASSF1A was observed in various stages of CRC. This inverse correlation was also observed in mCRC cells lines (T84, Colo 205) treated with Akt inhibitor. Inhibition of FoxM1 expression in mCRC cells as well as in our ex vivo model resulted in increased RASSF1A expression. Reduced levels of RASSF1A expression were found in normal cells (RWPE-1, HBEpc, MCF10A, EC) stimulated with exogenous VEGF 165 . Downregulation of FoxM1 also coincided with increased YAP phosphorylation, indicative of tumor suppression. Conversely, downregulation of RASSF1A coincided with FoxM1 overexpression. These studies have identified for the first time an integrated signaling pathway between FoxM1 and RASSF1A in mCRC progression, which may facilitate the development of novel therapeutic options for advanced colon cancer therapy. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.en_US
dc.description.sponsorshipWe wish to thank the Department of Pediatrics at the University of Maryland School of Medicine for support.en_US
dc.description.urihttps://dx.doi.org/10.3390/cancers11020199en_US
dc.language.isoen_USen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofCancers
dc.subjectCancer organoidsen_US
dc.subjectFoxM1en_US
dc.subjectMetastatic colon cancer (mCRC)en_US
dc.subjectP-YAPen_US
dc.subjectRASSF1Aen_US
dc.titleIdentification of cross talk between FoxM1 and RASSF1A as a therapeutic target of colon canceren_US
dc.typeArticleen_US
dc.identifier.doi10.3390/cancers11020199


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