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

Xiuwen Yan, Nengqi Cao, Yeh Chen, Hsin Yi Lan, Jong Ho Cha, Wen Hao Yang*, Muh Hwa Yang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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.

Original languageEnglish
Pages (from-to)1009-1014
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number4
StatePublished - 19 Feb 2020


  • Amoeboid movement
  • Cell motility
  • FaDu
  • Invadopodia
  • MT4-MMP


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