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Int J Biochem Cell Biol. 2016 Jan;70:161-72. doi: 10.1016/j.biocel.2015.11.015. Epub 2015 Nov 29.

Vimentin-mediated regulation of cell motility through modulation of beta4 integrin protein levels in oral tumor derived cells.

Author information

1
Cancer Research Institute (CRI), Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre (TMC), Kharghar, Navi Mumbai, India.
2
Gade Laboratory for Pathology, Institute of Clinical Medicine, University of Bergen, Norway; Department of Pathology, Haukeland University Hospital, Bergen, Norway.
3
Surgical Oncology, Head and Neck Unit, Tata Memorial Hospital (TMH), Parel, Mumbai, India.
4
Department of Pathology, Tata Memorial Hospital (TMH), Parel, Mumbai, India.
5
Laboratory of Neurochemistry, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
6
Cancer Research Institute (CRI), Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre (TMC), Kharghar, Navi Mumbai, India. Electronic address: mvaidya@actrec.gov.in.

Abstract

Vimentin expression correlates well with migratory and invasive potential of the carcinoma cells. The molecular mechanism by which vimentin regulates cell motility is not yet clear. Here, we addressed this issue by depleting vimentin in oral squamous cell carcinoma derived cell line. Vimentin knockdown cells showed enhanced adhesion and spreading to laminin-5. However, we found that they were less invasive as compared to the vector control cells. In addition, signaling associated with adhesion behavior of the cell was increased in vimentin knockdown clones. These findings suggest that the normal function of β4 integrin as mechanical adhesive device is enhanced upon vimentin downregulation. As a proof of principle, the compromised invasive potential of vimentin depleted cells could be rescued upon blocking with β4 integrin adhesion-blocking (ASC-8) antibody or downregulation of β4 integrin in vimentin knockdown background. Interestingly, plectin which associates with α6β4 integrin in the hemidesmosomes, was also found to be upregulated in vimentin knockdown clones. Furthermore, experiments on lysosome and proteasome inhibition revealed that perhaps vimentin regulates the turnover of β4 integrin and plectin. Moreover, an inverse association was observed between vimentin expression and β4 integrin in oral squamous cell carcinoma (OSCC). Collectively, our results show a novel role of vimentin in modulating cell motility by destabilizing β4 integrin-mediated adhesive interactions. Further, vimentin-β4 integrin together may prove to be useful markers for prognostication of human oral cancer.

KEYWORDS:

Cell adhesion; Migration; OSCC; Vimentin; β4 integrin

PMID:
26646105
DOI:
10.1016/j.biocel.2015.11.015
[Indexed for MEDLINE]

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