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

ABSTRACT: Recently, endolysosomal cation channels have emerged as an attractive anti-cancer target: namely the mucolipin subfamily of transient potential receptors (TRPMLs), which comprises three isoforms – TRPML1 (MCOLN1), TRPML2 (MCOLN2), and TRPML3 (MCOLN3). TRPML1, the most intensively researched member of the family, is ubiquitously expressed in the membranes of endosomes and lysosomes, whereas TRPML2 and TRPML3 are mainly localized in specialized cells (e. g. immune cells, hair cells of the inner ear, secretory cells, and melanocytes). In past research TRPML1 has been linked to ion homeostasis, vesicular trafficking, and autophagy. Aside from these physiological functionalities, TRPML1’s role in cancer is emerging. Interestingly, it has been implicated to regulate cancer cell migration as its inhibition reduces invasiveness of breast cancer cells in vitro and in vivo. However, the underlying mechanism is still vastly elusive. Given the apparent correlation between TRPML1 and cancer cell migration, we aimed to further elucidate its role in cancer cell migration in hepatocellular carcinoma and, most importantly, uncover the underlying mechanisms by monitoring cell-junctional and cell-adhesion proteins.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Jan Bernd Stöckl  

LAB HEAD: Thomas Fröhlich

PROVIDER: PXD046212 | Pride | 2024-03-20

REPOSITORIES: Pride