RT Journal Article
SR Electronic
T1 CLIC3 controls recycling of late endosomal MT1-MMP and dictates invasion and metastasis in breast cancer
JF Journal of Cell Science
JO J. Cell Sci.
FD The Company of Biologists Ltd
SP 3893
OP 3901
DO 10.1242/jcs.135947
VO 127
IS 18
A1 Macpherson, Iain R.
A1 Rainero, Elena
A1 Mitchell, Louise E.
A1 van den Berghe, Peter V. E.
A1 Speirs, Claire
A1 Dozynkiewicz, Marta A.
A1 Chaudhary, Suman
A1 Kalna, Gabriela
A1 Edwards, Joanne
A1 Timpson, Paul
A1 Norman, Jim C.
YR 2014
UL http://jcs.biologists.org/content/127/18/3893.abstract
AB Chloride intracellular channel 3 (CLIC3) drives invasiveness of pancreatic and ovarian cancer by acting in concert with Rab25 to regulate the recycling of α5β1 integrin from late endosomes to the plasma membrane. Here, we show that in two estrogen receptor (ER)-negative breast cancer cell lines, CLIC3 has little influence on integrin recycling, but controls trafficking of the pro-invasive matrix metalloproteinase MT1-MMP (also known as MMP14). In MDA-MB-231 cells, MT1-MMP and CLIC3 are localized primarily to late endosomal/lysosomal compartments located above the plane of adhesion and near the nucleus. MT1-MMP is transferred from these late endosomes to sites of cell–matrix adhesion in a CLIC3-dependent fashion. Correspondingly, CLIC3-knockdown opposes MT1-MMP-dependent invasive processes. These include the disruption of the basement membrane as acini formed from MCF10DCIS.com cells acquire invasive characteristics in 3D culture, and the invasion of MDA-MB-231 cells into Matrigel or organotypic plugs of type I collagen. Consistent with this, expression of CLIC3 predicts poor prognosis in ER-negative breast cancer. The identification of MT1-MMP as a cargo of a CLIC3-regulated pathway that drives invasion highlights the importance of late endosomal sorting and trafficking in breast cancer.