Rab11-FIP2 promotes colorectal cancer migration and invasion by regulating PI3K/AKT/MMP7 signaling pathway
Autor: | Xuanping Xia, Chenwei Pan, Bo Zheng, Changlong Xu, Shao Xiaoxiao, Shou-Xing Yang, Shenglong Xia, Jian-zhang Wang |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Biophysics Biology Biochemistry Metastasis Phosphatidylinositol 3-Kinases 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Cell Movement Cell Line Tumor medicine Humans Neoplasm Invasiveness Molecular Biology Protein kinase B PI3K/AKT/mTOR pathway Membrane Proteins Cell migration Cell Biology Transfection medicine.disease Cell biology Gene Expression Regulation Neoplastic 030104 developmental biology rab GTP-Binding Proteins Tumor progression Matrix Metalloproteinase 7 030220 oncology & carcinogenesis Signal transduction Carrier Proteins Colorectal Neoplasms Proto-Oncogene Proteins c-akt Signal Transduction |
Zdroj: | Biochemical and Biophysical Research Communications. 470:397-404 |
ISSN: | 0006-291X |
Popis: | Rab11-family interacting proteins (Rab11-FIPs) belong to an evolutionarily conserved protein family and act as effector molecules for the Rab11 family of small GTPases. Recent evidence suggests that Rab11-FIPs have important roles in tumor progression and metastasis. However, the contribution of Rab11-FIPs to colorectal carcinoma (CRC) remains elusive. Our study focuses on elucidating the role of Rab11-FIP2 in the migration and invasion of colorectal cancer cells. We firstly found upregulation of Rab11-FIP2 in CRC tissues compared with peritumor tissues by oncomine data-mining analysis, western blot analysis and immunohistochemistry (IHC) analysis, respectively. Then, we demonstrated that knockdown of Rab11-FIP2 via siRNAs transfection resulted in a decrease in migration and invasion of CRC cells, while overexpression of Rab11-FIP2 via lentiviral infection increased migration and invasion of CRC cells. In addition, we verified that Rab11-FIP2 promoted migration and invasion of CRC cells through upregulating MMP7 expression. Finally, using several kinase inhibitors, our results showed that Rab11-FIP2 regulated MMP7 expression through activating PI3K/Akt signaling. Our data suggested a potential role of Rab11-FIP2 in tumor progression and provided novel insights into the mechanism of how Rab11-FIP2 positively regulated cell migration and invasion in CRC cells. |
Databáze: | OpenAIRE |
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