Pacsin 2-dependent N-cadherin internalization regulates the migration behaviour of malignant cancer cells
| Autor: | Haymar Wint, Jianzhen Li, Tadashi Abe, Hiroshi Yamada, Takumi Higaki, Yasutomo Nasu, Masami Watanabe, Kohji Takei, Tetsuya Takeda |
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| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Journal of Cell Science. 136 |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.260827 |
| Popis: | Collective cell migration is the coordinated movement of multiple cells connected by cadherin-based adherens junctions and is essential for physiological and pathological processes. Cadherins undergo dynamic intracellular trafficking, and their surface level is determined by a balance between endocytosis, recycling and degradation. However, the regulatory mechanism of cadherin turnover in collective cell migration remains elusive. In this study, we show that the Bin/amphiphysin/Rvs (BAR) domain protein pacsin 2 (protein kinase C and casein kinase substrate in neurons protein 2) plays an essential role in collective cell migration by regulating N-cadherin (also known as CDH2) endocytosis in human cancer cells. Pacsin 2-depleted cells formed cell–cell contacts enriched with N-cadherin and migrated in a directed manner. Furthermore, pacsin 2-depleted cells showed attenuated internalization of N-cadherin from the cell surface. Interestingly, GST pull-down assays demonstrated that the pacsin 2 SH3 domain binds to the cytoplasmic region of N-cadherin, and expression of an N-cadherin mutant defective in binding to pacsin 2 phenocopied pacsin 2 RNAi cells both in cell contact formation and N-cadherin endocytosis. These data support new insights into a novel endocytic route of N-cadherin in collective cell migration, highlighting pacsin 2 as a possible therapeutic target for cancer metastasis. |
| Databáze: | OpenAIRE |
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