miR-200s Target Sec23a to Promote Breast CA Metastasis

Suppression of Sec23a lowers secretion of metastasis-suppressive proteins in mice

FRIDAY, Aug. 12 (HealthDay News) -- A new role has been suggested for micro-RNA (miR)-200s in breast cancer metastasis, involving suppression of Sec23a, thereby inhibiting Sec23a-dependent regulation of tumor secretome, according to an experimental study published online Aug. 7 in Nature Medicine.

Manav Korpal, from Princeton University in New Jersey, and colleagues investigated the pro-metastatic role of miR-200s in clinical and experimental models of breast cancer metastasis in 6-week-old mice. A retrospective analysis was performed on a series of 210 breast tumor samples, and on lung metastases and primary tumors. The results were confirmed by in vivo functional analysis.

The investigators found that expression of miR-200s in breast cancer was correlated with poor distant relapse-free survival in estrogen receptor-positive tumors, and profiling showed that expression of miR-200 was greater in lung metastases than in primary tumors. Based on genomic and proteomic analyses, overexpression of miR-200s was associated with a global shift in gene expression toward highly metastatic cells. Functional and clinical correlation studies demonstrated that miR-200s directly target genes at the RNA and protein level, including Sec23a. miR-200 overexpression suppresses Sec-23a-mediated secretion, thereby disrupting secretion of metastasis-suppressive proteins, including Igfbp4 and Tinagl1.

"We showed that miR-200s promote metastatic colonization by enhancing cell-intrinsic epithelial traits via the Zeb-E-cadherin axis and by inhibiting Sec23a-dependent regulation of tumor secretome. The fact that miR-200 targeting of Sec23a seems to have dichotomous roles in metastasis, hindering early steps of migration and invasion while promoting the late step of metastatic colonization, may explain the contradictory roles of miR-200s in various models of metastasis," the authors write.

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Physician’s Briefing Staff

Physician’s Briefing Staff

Published on August 12, 2011

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