Melanoma cell adhesion molecule (MCAM) mediates microtentacle generation, homotypic clustering, and reattachment of non-adherent breast tumor cells

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BACKGROUND: Melanoma cell adhesion molecule (MCAM) was first identified in advanced primary tumors and metastatic lesions. MCAM expression has been shown in previous studies to promote aggressive cancer phenotypes, including migration, invasion, tumorigenesis, and induction of vimentin and slug, indicative of EMT. Furthermore, overexpression of MCAM has been linked to poor prognosis and aggressive metastatic phenotypes, particularly in triple-negative breast cancer (TNBC). Early work has shown that MCAM can alter the actomyosin cytoskeleton and intermediate filaments; however, the impact of MCAM on the microtubule network and non-adherent cells has not been well studied. METHODS: Utilizing MCF-10A breast epithelial cell line engineered to overexpress MCAM and CRISPR MCAM knockouts in TNBC cell lines, we assessed the impact of MCAM on tubulin-driven cytoskeletal phenotypes in non-adherent conditions. TetherChip technology, xCelligence RTCA, and immunoblotting techniques were utilized to investigate the impact of MCAM overexpression. RESULTS: Our results show that MCAM overexpression increases vimentin protein levels, α-tubulin post-translational modificaitons (PTMs), microtentacle (McTN) protrusions, homotypic cell clustering, cellular reattachment, and migration. These phenotypic increases can be inhibited with FDA-approved vinorelbine treatment. Conversely, the knockout of MCAM in TNBC cell lines sustains decreases of acetylated α-tubulin, implicating that MCAM expression may alter the microtubule cytoskeleton's stability directly. Knockout (KO) of MCAM also decreased microtentacle protrusions and McTN-supported phenotypes of homotypic cell clustering and cellular reattachment. Migration was also decreased in TNBC with MCAM KO. CONCLUSIONS: These findings suggest that MCAM can function through the microtubules in TNBC to impact McTN-supported phenotypes of homotypic cell clustering and cellular reattachment in non-adherent breast tumor cells.

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