Pancreatic tumor cell metastasis is restricted by MT1-MMP binding protein MTCBP-1

Li Qiang, Hong Cao, Jing Chen, Shaun G. Weller, Eugene W. Krueger, Lizhi Zhang, Gina L. Razidlo, Mark A. McNiven

Research output: Contribution to journalArticle

7 Scopus citations


The process by which tumor cells mechanically invade through surrounding stroma into peripheral tissues is an essential component of metastatic dissemination. The directed recruitment of the metalloproteinase MT1-MMP to invadopodia plays a critical role in this invasive process. Here, we provide mechanistic insight into MT1-MMP cytoplasmic tail binding protein 1 (MTCBP-1) with respect to invadopodia formation, matrix remodeling, and invasion by pancreatic tumor cells. MTCBP-1 localizes to invadopodia and interacts with MT1-MMP. We find that this interaction displaces MT1-MMP from invadopodia, thereby attenuating their number and function and reducing the capacity of tumor cells to degrade matrix. Further, we observe an inverse correlation between MTCBP-1 and MT1-MMP expression both in cultured cell lines and human pancreatic tumors. Consistently, MTCBP-1–expressing cells show decreased ability to invade in vitro and metastasize in vivo. These findings implicate MTCBP-1 as an inhibitor of the metastatic process.

Original languageEnglish (US)
Pages (from-to)317-332
Number of pages16
JournalJournal of Cell Biology
Issue number1
StatePublished - Jan 1 2019

ASJC Scopus subject areas

  • Cell Biology

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