Wnt Signaling in Cancer

Abstract

Stringent regulation of the Wnt pathways components and modulators is indispensable for the restoration of tissue homeostasis and development. The Wnt/β-catenin-dependent canonical pathway is the most comprehensively introspected Wnt signaling pathway which relies upon Frizzled receptor activation and cytosolic β-catenin stabilization followed by their nuclear transport and subsequent transcriptional activation of multiple target genes to influence multiple cellular processes. The β-catenin-independent noncanonical pathway is the alternative Wnt signaling pathway which operates through either planar cell polarity [PCP] or calcium-signaling mechanism to modulate gene regulation. These pathways are highly branched and interconnected to modulate downstream mechanisms individually or in a concerted fashion. Aberrant Wnt signaling induced by genetic or epigenetic impetus leads to carcinogenesis and metastasis; evidently, several cancer types have depicted alterations in multiple Wnt pathway components to render them as potential targets for anticancer chemotherapy. Several small molecules and biologicals antagonizing the Wnt signaling are currently undergoing through different stages of clinical trial for customizing efficacious as well as safe anticancer therapeutics. However, the healthy cells are also susceptible to blockage of Wnt signaling pathways as potential side effects that pose inherent challenge to the strategy which needs to be dealt with utmost precaution. Cancer-specific Wnt markers and combination of multiple therapeutic strategies can overcome the limitation which lies at the focus of the ongoing oncotherapeutic introspections. © Springer Nature Singapore Pte Ltd. 2022.