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Cell November 6, 2014; 159 (4): 844-56.
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A noncanonical Frizzled2 pathway regulates epithelial-mesenchymal transition and metastasis.

Gujral TS , Chan M , Peshkin L , Sorger PK , Kirschner MW , MacBeath G .

Wnt signaling plays a critical role in embryonic development, and genetic aberrations in this network have been broadly implicated in colorectal cancer. We find that the Wnt receptor Frizzled2 (Fzd2) and its ligands Wnt5a/b are elevated in metastatic liver, lung, colon, and breast cancer cell lines and in high-grade tumors and that their expression correlates with markers of epithelial-mesenchymal transition (EMT). Pharmacologic and genetic perturbations reveal that Fzd2 drives EMT and cell migration through a previously unrecognized, noncanonical pathway that includes Fyn and Stat3. A gene signature regulated by this pathway predicts metastasis and overall survival in patients. We have developed an antibody to Fzd2 that reduces cell migration and invasion and inhibits tumor growth and metastasis in xenografts. We propose that targeting this pathway could provide benefit for patients with tumors expressing high levels of Fzd2 and Wnt5a/b.

PubMed ID: 25417160
PMC ID: PMC4243058
Article link: Cell
Grant support: [+]

Species referenced: Xenopus
Genes referenced: akt1 cdh1 dvl2 foxc1 fyn fzd2 hoxb7 itk map2k1 mapk1 ocln snai2 stat3.1 stat3.2 vim wnt5a wnt5b

Article Images: [+] show captions
References [+] :
Balanis, Epithelial to mesenchymal transition promotes breast cancer progression via a fibronectin-dependent STAT3 signaling pathway. 2013, Pubmed