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Proteolipid Protein 2: A Potential Driver of Collective Cell Migration in Progressive Colon Cancer Epithelium
Author(s) -
Ghosh Dipanjana,
Datta Sunando
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.05072
Subject(s) - biology , epithelium , microbiology and biotechnology , cell , cell migration , cytoplasm , colorectal cancer , transmembrane protein , cytoskeleton , cancer , genetics , receptor
Collective cell migration (CCM), where cell‐cell integrity remained preserved during the movement, plays an important role in developmental physiology as well as in the progression of cancer. In epithelial cancers like the colorectal one, collective movement was reported amongst the cells. However, studies describing CCM in colorectal cancer (CRC) progression are majorly focused on the effect of extracellular tissue components on moving cell plasticity. The molecular and cellular mechanisms of CCM during CRC progression remained less explored. Here we report proteolipid protein 2 (PLP2), a colonic epithelium enriched transmembrane protein for its role in CCM. PLP2 was first discovered as a colonic epithelium enriched protein in a highly differentiated CRC cell line and was found to possess an expression gradient along the colonic crypt in normal individuals. Latter studies have reported its role in progression of several other cancer types. However, the underlying mechanism through which PLP2 drives CRC progression, remained elusive. Our data indicates that PLP2 shows a dynamic localization between cell‐cell junction (CCJ) and migrating edges during collective migration of a CRC epithelium. It was found to be involved in CCM, as demonstrated by live‐cell video‐microscopy followed by analysis based on particle image velocimetry (PIV) and individual cell tracking. During CCM, PLP2 was found to spatiotemporally colocalize with the cytoskeletal adaptor ZO‐1 to which it associates via its cytoplasmic C‐terminus. The association was further found to be involved in the positioning of ZO‐1 at the migrating edges and alters actin cytoskeletal organization during CCM, that involves Rac1 activation. Together our findings demonstrate that PLP2 drives the leading‐edge cell dynamics during collective migration of progressive CRC epithelium, via ZO‐1 mediated actin cytoskeletal remodeling and thereby opened up new avenues of cancer research.