MT4-MMP promotes invadopodia formation and cell motility in FaDu head and neck cancer cells.

MT4-MMP promotes invadopodia formation and cell motility in FaDu head and neck cancer cells.:

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MT4-MMP promotes invadopodia formation and cell motility in FaDu head and neck cancer cells.

Biochem Biophys Res Commun. 2019 Dec 05;:

Authors: Yan X, Cao N, Chen Y, Lan HY, Cha JH, Yang WH, Yang MH

Abstract

Hypoxia-inducible factor-1α (HIF-1α) induces cancer metastasis. We previously demonstrated that HIF-1α-induced membrane-type 4 matrix metalloproteinase (MT4-MMP) is involved in hypoxia-mediated metastasis in head and neck squamous cell carcinoma (HNSCC). However, the functions and detailed mechanisms of MT4-MMP in cancer metastasis are not well understood. In this study, we investigated whether MT4-MMP regulates invadopodia formation or individual cell movement-both critical to cancer migration and invasion-in three-dimensional (3D) environments. By expressing MT4-MMP in the HNSCC cell line FaDu, we demonstrated that MT4-MMP increases invadopodia formation and gelatin degradation. Furthermore, the amoeboid-like cell movement on collagen gel was increased by MT4-MMP expression in FaDu cells. Mechanistically, MT4-MMP may induce invadopodia formation by binding with Tks5 and PDGFRα to result in Src activation and promote amoeboid-like movement by stimulating the small GTPases Rho and Cdc42. Altogether, our data indicate that MT4-MMP induces two crucial mechanisms of cancer dissemination, invadopodia formation and amoeboid movement, and elucidate the prometastatic role of MT4-MMP in hypoxia-mediated cancer metastasis.

PMID: 31813546 [PubMed - as supplied by publisher]