Elevated expression of Wnt5a is associated with
malignancy, cell invasion, and
metastasis. The role of Wnt5a expression in
breast cancer remains elusive. We investigated the significance of Wnt5a expression in
breast cancer. The relationship between Wnt5a expression and clinicopathologic factors was assessed in invasive
breast cancer (n = 178) resected at Hiroshima University Hospital between January 2011 and February 2014. Wnt5a was expressed in 69 of 178 cases (39%) of invasive
breast cancer and correlated strongly with
estrogen receptor (ER) expression (P < 0.001). Wnt5a expression in ER-positive
breast cancer correlated significantly with
lymph node metastasis, nuclear grade, and lymphatic invasion. The recurrence-free survival was shorter in
breast cancer patients with Wnt5a expression than in those without (P = 0.024). The migratory capacity of ER-positive
breast cancer cells increased with constitutive expression of Wnt5a and decreased with Wnt5a knockdown.
DNA microarray analysis identified
activated leukocyte cell adhesion molecule (
ALCAM) as the primary gene induced by Wnt5a.
ALCAM was expressed in 69% of Wnt5a-positive but only 27% of Wnt5a-negative
cancers (κ = 0.444; P < 0.001). The inhibition of
ALCAM reversed the enhanced migratory effect of Wnt5a, confirming the importance of this
protein in the migration of ER-positive
breast cancer cells. Wnt5a expression is related to high
malignancy and a poor prognosis in ER-positive
breast cancer. We suspect that Wnt5a expression increases the
malignancy of
breast cancer by increasing the migratory capacity of
cancer cells through the induction of
ALCAM expression.