Expression of Wnt-5a is correlated with aggressiveness of gastric cancer by stimulating cell migration and invasion.
Wnt-5a is a representative ligand that activates a beta-catenin-independent pathway in the Wnt signaling. Although abnormal activation of beta-catenin-dependent pathway is often observed in human cancer, the relationship between beta-catenin-independent pathway and tumorigenesis is not clear. We sought to clarify how Wnt-5a is involved in aggressiveness of gastric cancer. Abnormal expression of Wnt-5a was observed in 71 of 237 gastric cancer cases by means of immunohistochemistry. The positivity of Wnt-5a expression was correlated with advanced stages and poor prognosis of gastric cancer. Wnt-5a had the abilities to stimulate cell migration and invasion in gastric cancer cells. Wnt-5a activated focal adhesion kinase and small GTP-binding protein Rac, both of which are known to play a role in cell migration. Cell migration, membrane ruffling, and turnover of paxillin were suppressed in Wnt-5a knockdown cells. Furthermore, anti-Wnt-5a antibody suppressed gastric cancer cell migration. These results suggest that Wnt-5a stimulates cell migration by regulating focal adhesion complexes and that Wnt-5a is not only a prognostic factor but also a good therapeutic target for gastric cancer.
Kurayoshi
Manabu
M
Department of Biochemistry, Hiroshima University, Hiroshima, Japan.
Oue
Naohide
N
Yamamoto
Hideki
H
Kishida
Michiko
M
Inoue
Atsuko
A
Asahara
Toshimasa
T
Yasui
Wataru
W
Kikuchi
Akira
A
D002465:Cell Movement; D049109:Cell Proliferation; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D009361:Neoplasm Invasiveness; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000502:physiology*; D013274:Stomach Neoplasms / Q000401:mortality / Q000473:pathology*; D051153:Wnt Proteins / Q000032:analysis / Q000502:physiology*; D000071818:Wnt-5a Protein
D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051416:Focal Adhesion Protein-Tyrosine Kinases; D048031:JNK Mitogen-Activated Protein Kinases