Inhibition of fascin in cancer and stromal cells blocks ovarian cancer metastasis

Gynecologic Oncology
Sean McGuireHilary A Kenny

Abstract

Ovarian cancer (OvCa) metastasis requires the coordinated motility of both cancer and stromal cells. Cellular movement is a dynamic process that involves the synchronized assembly of f-actin bundles into cytoskeletal protrusions by fascin. Fascin directly binds f-actin and is an integral component of filopodia, lamellapodia and stress fibers. Here, we examine the expression pattern and function of fascin in the cancer and stromal cells of OvCa tumors. Fascin expression was evaluated in human cells and tissues using immunohistochemistry and immunofluorescence. The functional role of fascin in cancer and stromal cells was assessed with in vitro functional assays, an ex vivo colonization assay and in vivo metastasis assays using siRNA/shRNA and an inhibitor. The effect of fascin inhibition on Cdc42 and Rac1 activity was evaluated using GTPase activity assays and immunofluorescence. Fascin expression was found to be higher in the stromal cell, when compared to the cancer cell, compartment of ovarian tumors. The low expression of fascin in the cancer cells of the primary tumor indicated a favorable prognosis for non-serous OvCa patients. In vitro, both knockdown and pharmacologic inhibition of fascin decreased the migration of cance...Continue Reading

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Citations

Jan 23, 2020·Cells·Marco Montagner, Sirio Dupont
Aug 21, 2020·The Journal of Biological Chemistry·Martin J BakerMarcelo G Kazanietz
Nov 12, 2020·Biology·Jaya Aseervatham
Feb 23, 2021·Molecular Therapy Oncolytics·Hongliang LiuWei Gao
Apr 28, 2020·Experimental Cell Research·Masato YoshiharaFumitaka Kikkawa

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