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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.

SUBMITTER: Astudillo P

PROVIDER: S-EPMC7064718 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Wnt5a Signaling in Gastric Cancer.

Astudillo Pablo P

Frontiers in cell and developmental biology 20200304

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, ca ...[more]

PMID: 32195251

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Project description:Purpose:Gastric cancer (GC) is a malignant disease of digestive tract. Clinically, radiation therapy is widely applied in treating GC, while with undesirable outcome due to tumor re-proliferation and recurrence and metastasis after radiation. Therefore, it is crucial to explore potential molecular mechanisms to develop therapeutic strategies. The present study found that miR-26a-5p has low expression in GC patients and could regulate Wnt5a to inhibit tumor growth, which was a potential therapeutic target for GC. To explore the expression and related mechanism of miR-26a-5p and Wnt5a in GC. Patients and Methods:MiR-26a-5p and Wnt5a were extracted from the transcriptome data of GC downloaded from TCGA database for analysis. The expression levels of miR-26a-5p and Wnt5a in patients' tissues and serum were detected by qRT-PCR, and their correlation with patients' pathological data and survival was analyzed. In addition, miR-26a-5p and Wnt5a overexpression and inhibition vectors were transfected into cells to observe the effects on the proliferation, invasion and apoptosis of GC cells. The relationship between miR-26a-5p and Wnt5a was analyzed by dual luciferase report. Results:The database and clinical samples showed that miR-26a-5p level was low while Wnt5a was high in GC. MiR-26a-5p level decreased in patients with stage III+IV, lymphatic metastasis and tumor ?3cm, and Wnt5a was contrary to that of the miR-26a-5p, with diagnostic value. Overexpressed miR-26a-5p and inhibited Wnt5a enhanced apoptosis, decreased proliferation and invasion, reduced Bcl-2 and ?-catenin proteins, and elevated Caspase 3, E-cadherin and Bax proteins, while inhibited miR-26a-5p and over-expressed Wnt5a showed the opposite results. Dual luciferase report confirmed that miR-26a-5p targeted to regulate Wnt5a, and rescue experiments found that these effects could be counteracted by reducing miR-26a-5p level. Conclusion:Overexpressed miR-26a-5p can inhibit Wnt5a expression, promote cell apoptosis, and suppress cell proliferation and invasion in GC.

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Wnt5a Signaling in Gastric Cancer.

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Wnt5a Signaling in Gastric Cancer.

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