Wnt5a Signaling in Cancer

Abstract

Wnt5a is involved in activating several non-canonical WNT signaling pathways, through binding to different members of the Frizzled- and Ror-family receptors. Wnt5a signaling is critical for regulating normal developmental processes, including proliferation, differentiation, migration, adhesion and polarity. However, the aberrant activation or inhibition of Wnt5a signaling is emerging as an important event in cancer progression, exerting both oncogenic and tumor suppressive effects. Recent studies show the involvement of Wnt5a in regulating cancer cell invasion, metastasis, metabolism and inflammation. In this article, we review findings regarding the molecular mechanisms and roles of Wnt5a signaling in various cancer types, and highlight Wnt5a in ovarian cancer.

Keywords: Wnt5a; cancer; epithelial-mesenchymal transition (EMT); frizzled (Fzd); inflammation; microenvironment; non-canonical Wnt signaling; ovarian cancer; receptor tyrosine kinase-like orphan receptor (Ror); senescence.

Figure 1

Overview of Wnt5a signaling in cancer. (A) Wnt5a binds to a number of distinct trans-membrane receptors to influence a diverse array of tumor cell behaviors; (B) Summary of Wnt5a effector proteins that influence cell behavior.

Figure 2

Wnt5a expression in human ovarian cancer. (A) Summary of WNT5A expression in human ovarian cancer. Data are obtained from The Cancer Genome Atlas (TCGA) and represent 583 ovarian cancer samples. Gene expression was measured using the Affymetrix microarray hgu133a. Data were normalized with gcrma and relative expression values (y-axis) are on a log2 scale [121]. Counts (x-axis) indicates the number of patients with a specific expression value x; (B) Analysis of Wnt5a protein levels in human ovarian cancer ascites. Ascites fluid was obtained from women with ovarian cancer. After centrifugation to remove cellular components, WNT5A levels were determined by ELISA using 100 uL of ascites. The mean concentration of WNT5A in ascites (n = 20) is 584.4 ± 190 ng/mL. Similar levels are expressed by cultured ovarian cancer cell lines (OvCa 429, OvCa433, DOV13, SKOV-i.p.; mean 354.4 ± 108.1 ng/mL).