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Mol Cancer Res. 2015 May;13(5):934-43. doi: 10.1158/1541-7786.MCR-14-0604. Epub 2015 Feb 12.

MAPK7 Regulates EMT Features and Modulates the Generation of CTCs.

Author information

1
Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts. Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts.
2
Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts.
3
Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts. Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts. BioMEMS Resource Center, Massachusetts General Hospital Center for Bioengineering in Medicine, Charlestown, Massachusetts.
4
BioMEMS Resource Center, Massachusetts General Hospital Center for Bioengineering in Medicine, Charlestown, Massachusetts. Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts.
5
Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts. Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts.
6
Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts. Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts. Howard Hughes Medical Institute, Chevy Chase, Maryland. haber@helix.mgh.harvard.edu.

Abstract

Epithelial-to-mesenchymal transition (EMT) has been implicated in models 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 knockdown 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.

IMPLICATIONS:

Suppression of MAPK7 induces epithelial markers, reduces generation of circulating tumor cells and appearance of lung metastases.

PMID:
25678598
PMCID:
PMC4433453
DOI:
10.1158/1541-7786.MCR-14-0604
[Indexed for MEDLINE]
Free PMC Article

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