Pals1 prevents Rac1-dependent colorectal cancer cell metastasis by inhibiting Arf6
| Autor: | Albrecht Schwab, Christin Emming, Zoltán Pethő, Rita Schröter, Anja K. Wege, Pavel I. Nedvetsky, Julia Harms, Justine Guske, Simona Mareike Lüttgenau, Ute Neugebauer, Michael P. Krahn, Katrin Weber, Olga Panichkina, Thomas Wagner, Florian Weber |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
rac1 GTP-Binding Protein Cancer Research Colorectal cancer Cell RAC1 Biology Metastasis 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation Cell Movement medicine Animals Humans Neoplasm Invasiveness Cell migration Arf6 Letter to the Editor Cytoskeleton RC254-282 Cancer Membrane Proteins Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease HCT116 Cells 030104 developmental biology medicine.anatomical_structure Oncology Pals1 ADP-Ribosylation Factor 6 030220 oncology & carcinogenesis Cancer cell Cancer research Molecular Medicine Heterografts Colorectal Neoplasms Nucleoside-Phosphate Kinase Rac1 |
| Zdroj: | Molecular Cancer, Vol 20, Iss 1, Pp 1-7 (2021) Molecular Cancer |
| ISSN: | 1476-4598 |
| Popis: | 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. Supplementary Information The online version contains supplementary material available at 10.1186/s12943-021-01354-2. |
| Databáze: | OpenAIRE |
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