Wnt5a Signaling in Gastric Cancer

Abstract

Gastric cancer remains an important health challenge, accounting for a significant number of cancer-related deaths worldwide. Therefore, a deeper understanding of the molecular mechanisms involved in gastric cancer establishment and progression is highly desirable. The Wnt pathway plays a fundamental role in development, homeostasis, and disease, and abnormal Wnt signaling is commonly observed in several cancer types. Wnt5a, a ligand that activates the non-canonical branch of the Wnt pathway, can play a role as a tumor suppressor or by promoting cancer cell invasion and migration, although the molecular mechanisms explaining these roles have not been fully elucidated. Wnt5a is increased in gastric cancer samples; however, most gastric cancer cell lines seem to exhibit little expression of this ligand, thus raising the question about the source of this ligand in vivo. This review summarizes available research about Wnt5a expression and signaling in gastric cancer. In gastric cancer, Wnt5a promotes invasion and migration by modulating integrin adhesion turnover. Disheveled, a scaffolding protein with crucial roles in Wnt signaling, mediates the adhesion-related effects of Wnt5a in gastric cancer cells, and several studies provide growing support for a model whereby Disheveled-interacting proteins mediates Wnt5a signaling to modulate cytoskeleton dynamics. However, Wnt5a might induce other effects in gastric cancer cells, such as cell survival and induction of gene expression. On the other hand, the available evidence suggests that Wnt5a might be expressed by cells residing in the tumor microenvironment, where feedback mechanisms sustaining Wnt5a secretion and signaling might be established. This review analyzes the possible functions of Wnt5a in this pathological context and discusses potential links to mechanosensing and YAP/TAZ signaling.

A Non-canonical Wnt Signature Correlates With Lower Survival in Gastric Cancer

“…It is worth noting that cases with high WNT5A and WNT2 expression partially overlap. Regarding WNT5A , its precise source in GC has not been defined ( Astudillo, 2020 ). For instance, some GC cell lines show low WNT5A levels, while cancer-associated fibroblasts (CAFs) or tumor-associated macrophages (TAMs) might secrete Wnt5a in the context of GC ( Zhao et al, 2013 ; Wang et al, 2016 ).…”

Critical role of miR‐26a‐5p/Wnt5a signaling in gambogic acid‐induced inhibition of gastric cancer

“…[ 27 ] Although the exact source of Wnt5a was still controversial, Wnt5a was believed to play a vital role in GC establishment and progression. [ 28 ] Our results demonstrated that downregulation of Wnt5a was involved in GA‐induced inhibition of GC cell growth and promotion of apoptosis, indicating miR‐26a‐5p/Wnt5a pathway would probably be a conserved signaling pathway in the regulation of GC growth.…”

Allicin Reduces 5-fluorouracil-resistance in Gastric Cancer Cells through Modulating MDR1, DKK1, and WNT5A Expression

“…High expression of WNT5A is associated with a poor prognosis. WNT5A may behave as a tumor suppressor or a tumor-promoting agent in cancers [29,30]. DKK1 may act as a tumor suppressor or an oncogene in different cancers.…”