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

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.

• Authors: Xiuwen Yan, Nengqi Cao, Yeh Chen, Hsin-Yi Lan, Jong-Ho Cha, Wen-Hao Yang, Muh-Hwa Yang
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 522 Issue 4 Pg. 1009-1014 (02 19 2020) ISSN: 1090-2104 [Electronic] United States
• PMID: 31813546 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Adaptor Proteins, Vesicular Transport
• Myosin Light Chains
• SH3PXD2A protein, human
• myosin light chain 2
• Phosphotyrosine
• Gelatin
• Receptor, Platelet-Derived Growth Factor alpha
• src-Family Kinases
• MMP17 protein, human
• Matrix Metalloproteinases, Membrane-Associated
• Cardiac Myosins
• cdc42 GTP-Binding Protein
• rho GTP-Binding Proteins

Topics

• Adaptor Proteins, Vesicular Transport (metabolism)
• Cardiac Myosins (metabolism)
• Cell Line, Tumor
• Cell Movement
• Gelatin (metabolism)
• HEK293 Cells
• Head and Neck Neoplasms (enzymology, pathology)
• Humans
• Matrix Metalloproteinases, Membrane-Associated (metabolism)
• Myosin Light Chains (metabolism)
• Neoplasm Invasiveness
• Phosphorylation
• Phosphotyrosine (metabolism)
• Podosomes (pathology)
• Protein Binding
• Receptor, Platelet-Derived Growth Factor alpha (metabolism)
• Signal Transduction
• cdc42 GTP-Binding Protein (metabolism)
• rho GTP-Binding Proteins (metabolism)
• src-Family Kinases (metabolism)