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Brasher MI, Chafe SC, McDonald PC, et al. Syntaxin4-Munc18c interaction promotes breast tumor invasion and metastasis by regulating MT1-MMP trafficking. Mol Cancer Res. 2021;doi: 10.1158/1541-7786.MCR-20-0527.
Brasher, M. I., Chafe, S. C., McDonald, P. C., Nemirovsky, O., Gorshtein, G., Gerbec, Z. J., Brown, W. S., Grafinger, O. R., Marchment, M., Matus, E., Dedhar, S., & Coppolino, M. G. (2021). Syntaxin4-Munc18c interaction promotes breast tumor invasion and metastasis by regulating MT1-MMP trafficking. Molecular cancer research : MCR, . https://doi.org/10.1158/1541-7786.MCR-20-0527
Brasher, Megan I, et al. "Syntaxin4-Munc18c interaction promotes breast tumor invasion and metastasis by regulating MT1-MMP trafficking." Molecular cancer research : MCR vol. (2021). doi: https://doi.org/10.1158/1541-7786.MCR-20-0527
Brasher MI, Chafe SC, McDonald PC, Nemirovsky O, Gorshtein G, Gerbec ZJ, Brown WS, Grafinger OR, Marchment M, Matus E, Dedhar S, Coppolino MG. Syntaxin4-Munc18c interaction promotes breast tumor invasion and metastasis by regulating MT1-MMP trafficking. Mol Cancer Res. 2021 Dec 07; doi: 10.1158/1541-7786.MCR-20-0527. Epub 2021 Dec 07. PMID: 34876482.
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Mol Cancer Res. 2021 Dec 07; doi: 10.1158/1541-7786.MCR-20-0527. Epub 2021 Dec 07.

Syntaxin4-Munc18c interaction promotes breast tumor invasion and metastasis by regulating MT1-MMP trafficking.

Molecular cancer research : MCR

Megan I Brasher, Shawn C Chafe, Paul C McDonald, Oksana Nemirovsky, Genya Gorshtein, Zachary J Gerbec, Wells S Brown, Olivia R Grafinger, Matthew Marchment, Esther Matus, Shoukat Dedhar, Marc G Coppolino

Affiliations

  1. Molecular and Cellular Biology, University of Guelph.
  2. Integrative Oncology, British Columbia Cancer Research Centre.
  3. Integrative Oncology, BC Cancer Research Institute.
  4. Biological Sciences, Sunnybrook Research Institute.
  5. University of Guelph.
  6. Department of Biochemistry & Molecular Biology, BC Cancer Research Centre.
  7. Molecular and Cellular Biology, University of Guelph [email protected].

PMID: 34876482 DOI: 10.1158/1541-7786.MCR-20-0527

Abstract

Invasion of neighboring extracellular matrix (ECM) by malignant tumor cells is a hallmark of metastatic progression. This invasion can be mediated by subcellular structures known as invadopodia, the function of which depends upon SNARE-mediated vesicular transport of cellular cargo. Recently, it has been shown the SNARE Syntaxin4 (Stx4) mediates trafficking of MT1-MMP to invadopodia, and that Stx4 is regulated by Munc18c in this context. Here, it is observed that expression of a construct derived from the N-terminus of Stx4, which interferes with Stx4-Munc18c interaction, leads to perturbed trafficking of MT1-MMP, and reduced invadopodium-based invasion in vitro, in models of triple negative breast cancer (TNBC). Expression of Stx4 N-terminus also led to increased survival and markedly reduced metastatic burden in multiple TNBC models in vivo. The findings are the first demonstration that disrupting Stx4-Munc18c interaction can dramatically alter metastatic progression in vivo, and suggest that this interaction warrants further investigation as a potential therapeutic target. Implications: Disrupting the interaction of Syntaxin4 and Munc18c may be a useful approach to perturb trafficking of MT1-MMP and reduce metastatic potential of breast cancers.

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