RGC32 induces epithelial-mesenchymal transition by activating the Smad/Sip1 signaling pathway in CRC

• Published in: Scientific reports Vol. 7; no. 1; p. 46078
• Main Authors: Wang, Xiao-Yan, Li, Sheng-Nan, Zhu, Hui-Fang, Hu, Zhi-Yan, Zhong, Yan, Gu, Chuan-Sha, Chen, Shi-You, Liu, Teng-Fei, Li, Zu-Guo
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 04.05.2017
• Subjects: Animals; Biomarkers, Tumor - metabolism; Cell adhesion & migration; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell growth; Cell Line, Tumor; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; E-cadherin; Epithelial-Mesenchymal Transition - genetics; Female; Gene Expression Regulation, Neoplastic; Humans; Invasiveness; Male; Mesenchyme; Metastasis; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Muscle Proteins - genetics; Muscle Proteins - metabolism; Neoplasm Invasiveness; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Pathology; Phenotype; Proteins; RNA-Binding Proteins - metabolism; Signal Transduction; Smad protein; Smad Proteins - metabolism; Survival Analysis; Tumor cells; Tumorigenesis; Tumors; Up-Regulation - genetics; Vimentin
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep46078

Response gene to complement 32 (RGC32) is a transcription factor that regulates the expression of multiple genes involved in cell growth, viability and tissue-specific differentiation. However, the role of RGC32 in tumorigenesis and tumor progression in colorectal cancer (CRC) has not been fully elucidated. Here, we showed that the expression of RGC32 was significantly up-regulated in human CRC tissues versus adjacent normal tissues. RGC32 expression was significantly correlated with invasive and aggressive characteristics of tumor cells, as well as poor survival of CRC patients. We also demonstrated that RGC32 overexpression promoted proliferation, migration and tumorigenic growth of human CRC cells in vitro and in vivo. Functionally, RGC32 facilitated epithelial-mesenchymal transition (EMT) in CRC via the Smad/Sip1 signaling pathway, as shown by decreasing E-cadherin expression and increasing vimentin expression. In conclusion, our findings suggested that overexpression of RGC32 facilitates EMT of CRC cells by activating Smad/Sip1 signaling.