Abstract：
: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.
journal_name
Celljournal_title
Cellauthors
Gujral TS,Chan M,Peshkin L,Sorger PK,Kirschner MW,MacBeath Gdoi
10.1016/j.cell.2014.10.032subject
Has Abstractpub_date
2014-11-06 00:00:00pages
844-56issue
4eissn
0092-8674issn
1097-4172pii
S0092-8674(14)01359-2journal_volume
159pub_type
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