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Mesenchymal splice isoform of CD44 (CD44s) promotes EMT/invasion and imparts stem‐like properties to ovarian cancer cells
Author(s) -
Bhattacharya Rahul,
Mitra Tulika,
Ray Chaudhuri Susri,
Roy Sib Sankar
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26504
Subject(s) - cd44 , ovarian cancer , cancer research , alternative splicing , cancer stem cell , biology , metastasis , downregulation and upregulation , cancer , splicing factor , gene isoform , mesenchymal stem cell , epithelial–mesenchymal transition , cancer cell , stem cell , microbiology and biotechnology , cell , gene , genetics
Abstract Increased metastasis and a precipitous recurrence contribute to the lethality of ovarian cancer (OC). Several molecular mechanisms including aberrant‐splicing have been closely associated with the extent of cancer progression. Numerous gene transcripts are differentially spliced in cancer cells, CD44 being one of them. CD44 splice isoforms contribute to the aggressiveness and gain of stem‐like properties in different cancer types, but their role in ovarian cancer remains to be elucidated. We observed augmented CD44 levels in human ovarian cancer patient samples correlated with enhanced expression of the mesenchymal spliced variant CD44s (standard) and a concurrent decrease in the epithelial variants (CD44v). Moreover, CD44s was upregulated upon TGFβ1‐induced EMT, which was mediated through the downregulation of the splicing factor, ESRP1. Furthermore, overexpression of this mesenchymal isoform in the OC cells induced EMT and invasion, followed by the gain of stem‐like characteristics and chemoresistance. Since all these phenomena render lethality to this disease type, CD44s can be attributed for playing a major role in deregulated‐splicing mediated ovarian cancer progression.