Wnt5a-induced cell migration is associated with the aggressiveness of estrogen receptor-positive breast cancer

Abstract

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.

PITPNA-AS1 abrogates the inhibition of miR-876-5p on WNT5A to facilitate hepatocellular carcinoma progression

“…Wnt family member 5A (WNT5A) is implicated in oncogenesis and several developmental processes. According to previous studies, WNT5A promote multiple cellular processes of cancers [33][34][35][36] . Accordingly, it was confirmed by our paper that PITPNA-AS1 modulated WNT5A expression by targeting miR-876-5p.…”

An update of Wnt signalling in endometrial cancer and its potential as a therapeutic target

“…In addition, recent work has demonstrated a role for two distinct Wnt5a isoforms, Wnt5a-short and Wnt5a-long, in colorectal cancer progression and active Wnt signalling (Huang et al 2017). It is unknown what isoform Foxy-5 is based upon, and prudence is required, particularly for breast cancer patients where an increase of Wnt5a and ROR receptors has been shown to have oncogenic properties (Henry et al 2015, Han et al 2018, Kobayashi et al 2018.…”

An Autocrine Wnt5a Loop Promotes NF-κB Pathway Activation and Cytokine/Chemokine Secretion in Melanoma

“…Previous studies have demonstrated that Wnt5a has a dual effect on the progression of various types of human cancer [10], indicating that this pathway is particularly dependent on the cellular context [7]. Wnt5a is considered to have a tumor-suppressive function in neuroblastoma [11], leukemia [12], ductal breast carcinomas [13], ER-positive breast cancer [14], colorectal cancer [15], and thyroid cancer [16]. On the other hand, a protumorigenic role for Wnt5a has been shown for T-cell leukemia [17], melanoma [18], gastric cancer [19], non-small-cell lung cancer [20], pancreatic cancer [21], and prostate cancer [22].…”