MAPK7 Regulates EMT Features and Modulates the Generation of CTCs

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD
  • Breast Neoplasms / blood
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / pathology*
  • Cadherins / biosynthesis
  • Cadherins / genetics
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Mitogen-Activated Protein Kinase 7 / genetics
  • Mitogen-Activated Protein Kinase 7 / metabolism*
  • Neoplastic Cells, Circulating / metabolism*
  • Neoplastic Cells, Circulating / pathology*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Transcriptome


  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • RNA, Small Interfering
  • MAPK7 protein, human
  • Mitogen-Activated Protein Kinase 7