The Wnt/beta-catenin pathway in adrenocortical development and cancer

Abstract

Signaling by the Wnt family of secreted glycolipoproteins plays key roles in embryonic development of organisms ranging from nematodes to mammals and is also implicated in several types of human cancers. Canonical Wnt signaling functions by regulating the translocation of β-catenin to the nucleus, where it controls key gene expression programs through interaction with Tcf/Lef and other families of transcription factors. Wnts can also act through non-canonical pathways that do not involve β-catenin activation, but implicate small GTPases/JNK kinase and intracellular calcium. Here we review recent studies that have revealed the expression of several components of Wnt/β-catenin signaling in the adrenal cortex and discovered a key role for this pathway in the regulation of proliferation/differentiation of progenitor cells and in tumorigenesis of that endocrine organ.

Integrating Genetics and Genomics in Primary Aldosteronism

“…69 The involvement of the Wnt/␤-catenin pathway in the development of adrenocortical carcinomas is now well established. [72][73][74] The presence of activating mutations in exons 3 and 5 of the CTNNB1 gene, which encodes ␤-catenin, has been described in a wide variety of human cancers, including adrenocortical tumors. 72,[75][76][77] These mutations prevent ␤-catenin phosphorylation and induce nucleocytoplasmic accumulation of the protein, resulting in constitutive activation of ␤-catenin target genes.…”

The next step: mechanisms driving adrenocortical carcinoma metastasis

“…Canonical Wnt signaling regulates the translocation of the membrane protein beta-catenin to the nucleus, where it controls key gene expression programs through interaction with Tcf/Lef and other transcription factors. In many types of cancer, the gene encoding beta-catenin (CTNNB1) is mutated in those nucleotides that encode phosphorylation sites targeting the protein for distruction (El Wakil & Lalli 2011). Tissier and coworkers first reported the presence of activating CTNNB1 mutations both in benign and malignant ACTs (Tissier et al 2005).…”

Szlaki molekularne w raku kory nadnercza — od wiedzy o sygnalizacji komórkowej do metod diagnostyki i leczenia

“…In the adrenal cortex, the Wnt/b-catenin cascade is involved in adrenal development and differentiation [48,49]. Abnormal functioning of this system may lead to adrenal tumourigenesis.…”

“…W korze nadnerczy, szlak Wnt/b-katenina bierze udział w rozwoju i różnicowaniu nadnerczy [48,49]. Nieprawidłowe funkcjonowanie tego systemu może prowadzić do rozwoju nowotworu nadnercza.…”