| Autor: |
Knight, Jennifer F., Sung, Vanessa Y.C., Kuzmin, Elena, Couzens, Amber L., de Verteuil, Danielle A., Ratcliffe, Colin D.H., Coelho, Paula P., Johnson, Radia M., Samavarchi-Tehrani, Payman, Gruosso, Tina, Smith, Harvey W., Lee, Wontae, Saleh, Sadiq M., Zuo, Dongmei, Zhao, Hong, Guiot, Marie-Christine, Davis, Ryan R., Gregg, Jeffrey P., Moraes, Christopher, Gingras, Anne-Claude, Park, Morag |
| Zdroj: |
Cell Reports; March 2018, Vol. 22 Issue: 12 p3191-3205, 15p |
| Abstrakt: |
Triple-negative breast cancers (TNBCs) display a complex spectrum of mutations and chromosomal aberrations. Chromosome 5q (5q) loss is detected in up to 70% of TNBCs, but little is known regarding the genetic drivers associated with this event. Here, we show somatic deletion of a region syntenic with human 5q33.2–35.3 in a mouse model of TNBC. Mechanistically, we identify KIBRAas a major factor contributing to the effects of 5q loss on tumor growth and metastatic progression. Re-expression of KIBRAimpairs metastasis in vivoand inhibits tumorsphere formation by TNBC cells in vitro. KIBRAfunctions co-operatively with the protein tyrosine phosphatase PTPN14to trigger mechanotransduction-regulated signals that inhibit the nuclear localization of oncogenic transcriptional co-activators YAP/TAZ. Our results argue that the selective advantage produced by 5q loss involves reduced dosage of KIBRA, promoting oncogenic functioning of YAP/TAZ in TNBC. |
| Databáze: |
Supplemental Index |
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