MAL2 and rab17 selectively redistribute invadopodia proteins to laterally-induced protrusions in hepatocellular carcinoma cells.

MAL2 (myelin and lymphocyte protein 2) and rab17 have been identified as hepatocellular carcinoma tumor suppressors. However, little is known how their functions in hepatic polarized protein sorting/trafficking translate into how they function in the epithelial-to-mesenchymal transition and/or the mesenchymal-to-epithelial transition in metastases. To investigate this, we expressed MAL2 and rab17 alone or together in hepatoma-derived Clone 9 cells (that lack endogenous MAL2 and rab17). Like MAL2, we found that rab17 expression led to the formation of actin- and cholesterol-dependent protrusions that correlated to its anti-oncogenic properties. MAL2 or rab17 selectively promoted the redistribution of invadopodia proteins to the protrusion tips that correlated with decreased matrix degradation. MAL2-mediated redistribution required a putative EVH1 recognition motif whereas rab17-mediated redistribution was GTP dependent. We also determined that MAL2 and rab17 interaction was GTP dependent, but not dependent on the MAL2 EVH1 recognition motifs, and that protrusions formed by their combined expression shared features of those induced by either alone. Finally, we report that MAL2 or rab17 can redirect trafficking of newly synthesized membrane proteins from the Golgi to the induced protrusions and that the EVH1 recognition motif was required in MAL2 and that rab17-mediated trafficking was GTP dependent.

Citation

Saniya S Davis, Lauren R Bassaro, Pamela L Tuma. MAL2 and rab17 selectively redistribute invadopodia proteins to laterally-induced protrusions in hepatocellular carcinoma cells. Molecular biology of the cell. 2025 Mar 01;36(3):ar26

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PMID: 39813085

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