ERK activation and nuclear signaling induced by the loss of cell/matrix adhesion stimulates anchorage-independent growth of ovarian cancer cells

Journal of Cellular Biochemistry
Adnan Al-AyoubiScott T Eblen

Abstract

Ovarian cancer metastasis involves the sloughing of epithelial cells from the ovary into the peritoneal cavity, where the cells can survive and proliferate in peritoneal ascites under anchorage-independent conditions. For normal epithelial cells and fibroblasts, cell adhesion to the extracellular matrix is required to prevent apoptosis and for proper activation and nuclear signaling of the ERK MAP kinase. The mechanisms of ERK regulation by adhesion have been determined by our lab and others. In this report, we elucidate a novel means of ERK regulation by cellular adhesion in ovarian cancer cells. We demonstrate that ERK and its activator MEK are robustly stimulated after cell detachment from a substratum in several ovarian cancer cell lines, but not a benign ovarian cell line, independent of serum and FAK or PAK activity. MEK and ERK activation was sustained for 48 h after detachment, while activation by serum or growth factors in adherent cells was transient. Re-attachment of suspended ovarian cells to fibronectin restored basal levels of MEK and ERK activity. ERK activity in suspended cells was dynamically controlled through an autocrine stimulatory pathway and prevalent phosphatase activity. Suspended cells demonstrated hig...Continue Reading

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Citations

Nov 3, 2012·The Journal of Biological Chemistry·Cuixia YangFeng Gao
Nov 17, 2009·Cellular Immunology·Irina S SmirnovaThomas G Forsthuber
Jun 24, 2020·Histochemistry and Cell Biology·Bastian CzogallaFabian Trillsch
Aug 21, 2015·World Journal of Gastroenterology : WJG·Yan-Ling ChenBayasi Guleng
Jan 16, 2021·Free Radical Biology & Medicine·Qian WangDongmei Lai

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