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Activation of Hippo Signaling by rhBMP‐2 Suppresses the Proliferation of Human Colorectal Cancer Cell
Author(s) -
Liu Yu Chuan,
Kim Soo Mi
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.610.6
Subject(s) - cyclin dependent kinase , hippo signaling pathway , cell growth , cdk inhibitor , cyclin dependent kinase 6 , cancer research , chemistry , cell cycle , microbiology and biotechnology , signal transduction , kinase , bone morphogenetic protein , cell , biology , biochemistry , gene
Despite that the use of recombinant human bone morphogenetic protein (rhBMP)‐2 has been debated for a decade due to its oncogenic characteristics. However, the underlying molecular mechanism and safety issues of rhBMP‐2 usage remain poorly understood. In this study, we investigated the effect of rhBMP‐2 and its signaling pathways involved in colorectal cancer cell (CRC) using HT‐29 and HT‐116 cells. RhBMP‐2 significantly inhibited proliferation of CRC cells in dose‐dependent by MTT assay. Cell cycle arrest in G1 phase was induced at 24h after rhBMP‐2 treatment. RhBMP‐2 also stimulated Smad4, p53 and p21 levels, and reduced cyclin D1, cyclin‐dependent kinase (CDK) 4 and CDK6 activities. On the other hand, rhBMP‐2 treatment resulted in reduced protein expression levels of poly (ADP‐ribose) polymerase (PARP) whereas those of cleaved PARP and cleaved caspase‐9 were significantly increased in CRC cells. In addition, rhBMP‐2 increased RASSF1, MST1, MST2, Mob1, LATS1, Sav1, and p‐YAP protein levels. Therefore, our results indicate that rhBMP‐2 suppresses CRC cell proliferation which is mediated via the hippo signaling pathway. Therefore, targeting BMP‐2 may constitute a potential therapeutic strategy for CRC. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .