title: MAPK7 Regulates EMT Features and Modulates the Generation of CTCs.
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.
  
  
  CONCLUSIONS
  Suppression of MAPK7 induces epithelial markers, reduces generation of circulating tumor cells and appearance of lung metastases.
authors: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts. Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts.
authors: Sarah
authors: S
authors: Javaid
authors: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts.
authors: Jianmin
authors: J
authors: Zhang
authors: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts.
authors: Gromoslaw A
authors: GA
authors: Smolen
authors: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts.
authors: Min
authors: M
authors: Yu
authors: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts. Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts.
authors: Ben S
authors: BS
authors: Wittner
authors: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts.
authors: Anurag
authors: A
authors: Singh
authors: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts.
authors: Kshitij S
authors: KS
authors: Arora
authors: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts.
authors: Marissa W
authors: MW
authors: Madden
authors: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts.
authors: Rushil
authors: R
authors: Desai
authors: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts.
authors: Matthew J
authors: MJ
authors: Zubrowski
authors: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts.
authors: Benjamin J
authors: BJ
authors: Schott
authors: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts. Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts.
authors: David T
authors: DT
authors: Ting
authors: 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.
authors: Shannon L
authors: SL
authors: Stott
authors: 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.
authors: Mehmet
authors: M
authors: Toner
authors: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts. Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts.
authors: Shyamala
authors: S
authors: Maheswaran
authors: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts. Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts.
authors: Toshi
authors: T
authors: Shioda
authors: Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts. Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts.
authors: Sridhar
authors: S
authors: Ramaswamy
authors: 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.
authors: Daniel A
authors: DA
authors: Haber
mesh_terms: D000818:Animals; D015703:Antigens, CD; D001943:Breast Neoplasms / Q000097:blood / Q000201:enzymology* / Q000473:pathology*; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D048054:Mitogen-Activated Protein Kinase 7 / Q000235:genetics / Q000378:metabolism*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D034741:RNA, Small Interfering; C481581:MAPK7 protein, human; D048054:Mitogen-Activated Protein Kinase 7