Axed MUC4 (MUC4/X) aggravates pancreatic malignant phenotype by activating integrin-β1/FAK/ERK pathway

Biochimica Et Biophysica Acta. Molecular Basis of Disease
Rahat JahanSurinder K Batra

Abstract

Alternative splicing is evolving as an eminent player of oncogenic signaling for tumor development and progression. Mucin 4 (MUC4), a type I membrane-bound mucin, is differentially expressed in pancreatic cancer (PC) and plays a critical role in its progression and metastasis. However, the molecular implications of MUC4 splice variants during disease pathogenesis remain obscure. The present study delineates the pathological and molecular significance of a unique splice variant of MUC4, MUC4/X, which lacks the largest exon 2, along with exon 3. Exon 2 encodes for the highly glycosylated tandem repeat (TR) domain of MUC4 and its absence creates MUC4/X, which is devoid of TR. Expression analysis from PC clinical samples revealed significant upregulation of MUC4/X in PC tissues with most differential expression in poorly differentiated tumors. In vitro studies suggest that overexpression of MUC4/X in wild-type-MUC4 (WT-MUC4) null PC cell lines markedly enhanced PC cell proliferation, invasion, and adhesion to extracellular matrix (ECM) proteins. Furthermore, MUC4/X overexpression leads to an increase in the tumorigenic potential of PC cells in orthotopic transplantation studies. In line with these findings, doxycycline-induced expr...Continue Reading

Citations

Mar 17, 2020·Clinical and Experimental Medicine·Jinyu YuYan Kong
Jun 4, 2020·Cancer Metastasis Reviews·Koelina GangulySurinder K Batra
Jan 19, 2020·Seminars in Immunology·Shailendra K GautamSurinder K Batra
Oct 8, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christopher M ThompsonSurinder K Batra

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