Endolysosomal TRPML1 channel regulates cancer cell migration by altering intracellular trafficking of E-cadherin and β₁-integrin.

ABSTRACT: Metastasis still accounts for 90% of all cancer-related death cases. An increase of cellular mobility and invasive traits of cancer cells mark two crucial prerequisites of metastasis. Recent studies highlight the involvement of the endolysosomal cation channel TRPML1 in cell migration. Our results identified a widely antimigratory effect upon loss of TRPML1 function in a panel of cell lines in vitro and reduced dissemination in vivo. As mode-of-action, we established TRPML1 as a crucial regulator of cytosolic calcium levels, actin polymerization, and intracellular trafficking of two promigratory proteins: E-cadherin and β₁-integrin. Interestingly, KO of TRPML1 differentially interferes with the recycling process of E-cadherin and β₁-integrin in a cell line-dependant m

SUBMITTER: Frey N 

PROVIDER: S-EPMC10825694 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature