[HTML][HTML] Seventh international workshop on the CCN family of genes

B Perbal, G Schäfer, C Croce, II Session… - J Cell Communicat …, 2014 - Springer
B Perbal, G Schäfer, C Croce, II Session, S Irvine
J Cell Communicat Signal., 2014Springer
Background: Epithelial-mesenchymal transition (EMT) and its reverse process,
mesenchymal-epithelial transition (MET), play key roles in regulating embryogenesis.
Recent studies have shown that aberrant EMT activation contributes to cancer progression
and metastasis. Links between EMT and the gain of stem cell properties have been
suggested in physiological and pathological situations. CCN family protein 6 (CCN6/WISP3)
is a novel tumor suppressor that regulates diverse cellular functions. Our previous studies …
Background
Epithelial-mesenchymal transition (EMT) and its reverse process, mesenchymal-epithelial transition (MET), play key roles in regulating embryogenesis. Recent studies have shown that aberrant EMT activation contributes to cancer progression and metastasis. Links between EMT and the gain of stem cell properties have been suggested in physiological and pathological situations. CCN family protein 6 (CCN6/WISP3) is a novel tumor suppressor that regulates diverse cellular functions. Our previous studies have shown the blockade of CCN6 by short hairpin RNA triggers EMT in benign breast epithelial cells, with decreased expression of epithelial marker E-cadherin and increased activation of corresponding transcriptional repressor, Zeb1 and Snail. Moreover, loss of CCN6 expression endows benign breast epithelial cells with growth factor-independent properties, such as cell survival and anoikis resistance. However, little is known regarding the functions of CCN6 overexpression in breast cancer progression.
Methods
We overexpressed CCN6 in breast cancer cell lines, MDA-MB-231 and SUM-159, which are aggressive, have mesenchymal-like features and low levels of endogenous CCN6. CCN6 provoked functions were studied in vitro by proliferation, motility and invasion assays. Aldehyde dehydrogenase (ALDH1) was used to identify and investigate CCN6 roles in human breast cancer stem cells in vitro and in the mammary fat pads of mice.
Results
We showed that overexpression of CCN6 inhibits cell proliferation, motility and invasion of breast cancer cells. Importantly, CCN6 overexpression in these cells led to phenotypic changes towards mesenchymal-epithelial transition (MET), characterized by loss of mesenchymal cell marker Vimentin and downregulation of transcriptional factor, Zeb1. CCN6 overexpression significantly reduced the stem cell population of MDA-MB-231 and SUM-159 breast cancer cells, as well as their ability to form primary and metastatic tumors in mice.
Conclusions
Our data suggest a novel function of CCN6 in regulating MET and reducing the stem cell population of aggressive breast cancer cells.
Springer