| First Author | Zhan J | Year | 2015 |
| Journal | Cancer Lett | Volume | 361 |
| Issue | 1 | Pages | 75-85 |
| PubMed ID | 25724625 | Mgi Jnum | J:219946 |
| Mgi Id | MGI:5630011 | Doi | 10.1016/j.canlet.2015.02.039 |
| Citation | Zhan J, et al. (2015) Kindlin-2 induced by TGF-beta signaling promotes pancreatic ductal adenocarcinoma progression through downregulation of transcriptional factor HOXB9. Cancer Lett 361(1):75-85 |
| abstractText | Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths with no effective therapeutics. Invasion and metastasis are the major characteristics of PDAC. However, mechanisms underlying PDAC invasion and metastasis are elusive. In this report, we found that Kindlin-2 is a target protein of transforming growth factor beta (TGF-beta) signaling and is upregulated by TGF-beta1 in PDAC cells. TGF-beta1-upregulated Kindlin-2 promotes PDAC cell growth, migration and invasion, whereas Kindlin-2 upregulates transforming growth factor receptor I (TbetaRI), a key component of TGF-beta signaling. Thereby Kindlin-2 and TGF-beta signaling constitute a positive feedback loop. Mechanistically, Kindlin-2 promotes PDAC progression by downregulation of HOXB9 and E-cadherin. For clinical relevance, enhanced expression of Kindlin-2 predicts a poor overall survival for PDAC patients. Gene expression levels of Kindlin-2, TGF-beta, TbetaRI and HOXB9 are all correlated with the overall survival of PDAC patients in an Oncomine dataset. Taken together, our findings demonstrated that TGF-beta1-induced Kindlin-2 expression promotes PDAC progression by downregulation of HOXB9 and E-cadherin. |
