MAPK7 Regulates EMT Features and Modulates the Generation of CTCs

作者：Javaid Sarah; Zhang Jianmin; Smolen Gromoslaw A; Yu Min; Wittner Ben S; Singh Anurag; Arora Kshitij S; Madden Marissa W; Desai Rushil; Zubrowski Matthew J; Schott Benjamin J; Ting David T; Stott Shannon L; Toner Mehmet; Maheswaran Shyamala; Shioda Toshi; Ramaswamy Sridhar; Haber Daniel A^*

来源：Molecular Cancer Research, 2015, 13(5): 934-943.

DOI：10.1158/1541-7786.MCR-14-0604

Epithelial-to-mesenchymal transition (EMT) has been implicated inmodels of tumor cell migration, invasion, and metastasis. In a search for candidate therapeutic targets to reverse this process, nontumorigenic MCF10A breast epithelial cells were infected with an arrayed lentiviral kinome shRNA library and screened for either suppression or enhancement of a 26-gene EMT RNA signature. No individual kinase gene knock down was sufficient to induce EMT. In contrast, grouped epithelial markers were induced by knockdown of multiple kinases, including mitogen activated protein kinase 7 (MAPK7). In breast cancer cells, suppression of MAPK7 increased E-cadherin (CDH1) expression and inhibited cell migration. In an orthotopic mouse model, MAPK7 suppression reduced the generation of circulating tumor cells and the appearance of lung metastases. Together, these observations raise the possibility that targeting kinases that maintain mesenchymal cell properties in cancer cells, such as MAPK7, may lessen tumor invasiveness.

• 出版日期2015-5