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 Razidlo, Mark A Mc Niven

Research output: Contribution to journalArticle

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Abstract

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
JournalThe Journal of cell biology
Volume218
Issue number1
DOIs
StatePublished - Jan 7 2019

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Matrix Metalloproteinase 14
Tail
Carrier Proteins
Neoplasm Metastasis
Neoplasms
Metalloproteases
Cultured Cells
Cell Line

ASJC Scopus subject areas

  • Cell Biology

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Pancreatic tumor cell metastasis is restricted by MT1-MMP binding protein MTCBP-1. / Qiang, Li; Cao, Hong; Chen, Jing; Weller, Shaun G.; Krueger, Eugene W.; Zhang, Lizhi; Razidlo, Gina; Mc Niven, Mark A.

In: The Journal of cell biology, Vol. 218, No. 1, 07.01.2019, p. 317-332.

Research output: Contribution to journalArticle

Qiang, Li ; Cao, Hong ; Chen, Jing ; Weller, Shaun G. ; Krueger, Eugene W. ; Zhang, Lizhi ; Razidlo, Gina ; Mc Niven, Mark A. / Pancreatic tumor cell metastasis is restricted by MT1-MMP binding protein MTCBP-1. In: The Journal of cell biology. 2019 ; Vol. 218, No. 1. pp. 317-332.
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