Sorting nexin 9 negatively regulates invadopodia formation and function in cancer cells

Nawal Bendris, Carrie J S Stearns, Carlos R. Reis, Jaime Rodriguez-Canales, Hui Liu, Agnieszka W. Witkiewicz, Sandra L. Schmid

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The ability of cancer cells to degrade the extracellular matrix and invade interstitial tissues contributes to their metastatic potential. We recently showed that overexpression of sorting nexin 9 (SNX9) leads to increased cell invasion and metastasis in animal models, which correlates with increased SNX9 protein expression in metastases from human mammary cancers. Here, we report that SNX9 expression is reduced relative to neighboring normal tissues in primary breast tumors, and progressively reduced in more aggressive stages of non-small-cell lung cancers. We show that SNX9 is localized at invadopodia where it directly binds the invadopodia marker TKS5 and negatively regulates invadopodia formation and function. SNX9 depletion increases invadopodia number and the local recruitment of MT1-MMP by decreasing its internalization. Together, these effects result in increased localized matrix degradation. We further identify SNX9 as a Src kinase substrate and show that this phosphorylation is important for SNX9 activity in regulating cell invasion, but is dispensable for its function in regulating invadopodia. The diversified changes associated with SNX9 expression in cancer highlight its importance as a central regulator of cancer cell behavior.

Original languageEnglish (US)
Pages (from-to)2804-2816
Number of pages13
JournalJournal of Cell Science
Volume129
Issue number14
DOIs
StatePublished - Jul 15 2016

Fingerprint

Sorting Nexins
Neoplasms
Breast Neoplasms
Neoplasm Metastasis
Matrix Metalloproteinase 14
Aptitude
src-Family Kinases
Podosomes
Non-Small Cell Lung Carcinoma
Extracellular Matrix
Animal Models
Phosphorylation

Keywords

  • Extracellular matrix
  • Invadopodia
  • MT1-MMP
  • SNX9
  • Src kinase
  • TKS5

ASJC Scopus subject areas

  • Cell Biology

Cite this

Sorting nexin 9 negatively regulates invadopodia formation and function in cancer cells. / Bendris, Nawal; Stearns, Carrie J S; Reis, Carlos R.; Rodriguez-Canales, Jaime; Liu, Hui; Witkiewicz, Agnieszka W.; Schmid, Sandra L.

In: Journal of Cell Science, Vol. 129, No. 14, 15.07.2016, p. 2804-2816.

Research output: Contribution to journalArticle

Bendris, Nawal ; Stearns, Carrie J S ; Reis, Carlos R. ; Rodriguez-Canales, Jaime ; Liu, Hui ; Witkiewicz, Agnieszka W. ; Schmid, Sandra L. / Sorting nexin 9 negatively regulates invadopodia formation and function in cancer cells. In: Journal of Cell Science. 2016 ; Vol. 129, No. 14. pp. 2804-2816.
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