Luttgenau, Simona Mareike and Emming, Christin and Wagner, Thomas and Harms, Julia and Guske, Justine and Weber, Katrin and Neugebauer, Ute and Schroeter, Rita and Panichkina, Olga and Petho, Zoltan and Weber, Florian and Schwab, Albrecht and Wege, Anja Kathrin and Nedvetsky, Pavel and Krahn, Michael P. (2021) Pals1 prevents Rac1-dependent colorectal cancer cell metastasis by inhibiting Arf6. MOLECULAR CANCER, 20 (1): 74. ISSN , 1476-4598
Full text not available from this repository. (Request a copy)Abstract
Loss of apical-basal polarity and downregulation of cell-cell contacts is a critical step during the pathogenesis of cancer. Both processes are regulated by the scaffolding protein Pals1, however, it is unclear whether the expression of Pals1 is affected in cancer cells and whether Pals1 is implicated in the pathogenesis of the disease. Using mRNA expression data and immunostainings of cancer specimen, we show that Pals1 is frequently downregulated in colorectal cancer, correlating with poorer survival of patients. We further found that Pals1 prevents cancer cell metastasis by controlling Rac1-dependent cell migration through inhibition of Arf6, which is independent of the canonical binding partners of Pals1. Loss of Pals1 in colorectal cancer cells results in increased Arf6 and Rac1 activity, enhanced cell migration and invasion in vitro and increased metastasis of transplanted tumor cells in mice. Thus, our data reveal a new function of Pals1 as a key inhibitor of cell migration and metastasis of colorectal cancer cells. Notably, this new function is independent of the known role of Pals1 in tight junction formation and apical-basal polarity.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | POLARITY; ACTIVATION; EXPRESSION; GTPASE; CRUMBS; Colorectal cancer; Metastasis; Cell migration; Pals1; Arf6; Rac1; Cytoskeleton |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde) Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Sep 2022 13:31 |
| Last Modified: | 07 Sep 2022 13:31 |
| URI: | https://pred.uni-regensburg.de/id/eprint/46826 |
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