AXIN1 and AXIN2 variants in gastrointestinal cancers

Abstract

Mutations in the APC (adenomatous polyposis coli) gene, which encodes a multi-functional protein with a well-defined role in the canonical Wnt pathway, underlie familial adenomatous polypsosis, a rare, inherited form of colorectal cancer (CRC) and contribute to the majority of sporadic CRCs. However, not all sporadic and familial CRCs can be explained by mutations in APC or other genes with well-established roles in CRC. The AXIN1 and AXIN2 proteins function in the canonical Wnt pathway, and AXIN1/2 alterations have been proposed as key defects in some cancers. Here, we review AXIN1 and AXIN2 sequence alterations reported in gastrointestinal cancers, with the goal of vetting the evidence that some of the variants may have key functional roles in cancer development.

Role of the Wnt/β-catenin pathway in gastric cancer: An in-depth literature review

“…Axin1 and Axin2 proteins negatively regulate the Wnt signaling pathway based in their roles as scaffolding proteins involved in the assembly of the b-catenin destruction complex. Therefore, mutations in their genes have been proposed as critical defects in some cancers [140] . Moreover, Axin2 is a transcriptional target of the LEF/TCF-b-catenin transcription factor complex [141] .…”

Interaction between Wnt/β-catenin pathway and microRNAs regulates epithelial-mesenchymal transition in gastric cancer (Review)

“…Axin is the scaffold protein in β-catenin degradation compound while both germline and somatic alterations in Axin1 or Axin2 genes have been affirmed in gastrointestinal cancers. Pan et al (88) set forth five SNPs (334 C>T, 874 C>T, 1,396 G>A, 1,690 C>T and 1,942 T>G) and frameshift mutations in Axin1 involved in GC, in the meantime, a highly mutable G mononucleotide repeat sequence on exon 7 of Axin2 continually had a frameshift mutation (1-bp deletion) in gastric cancer with microsatellite instability (MSI) and nuclear β-catenin stabilization (89). Thus, devoting our efforts to the regulation on Wnt/β-catenin pathway in GC will notably benefit anti-metastatic approaches in the clinic.…”

AXIN1 protects against testicular germ cell tumors via the PI3K/AKT/mTOR signaling pathway

“…The functional role of axis inhibition protein 1 (AXIN1), a multi-domain scaffold protein, has been associated with the tumorigenesis and progression of a number of diseases, including hepatitis B virus-related hepatocellular carcinoma and gastrointestinal cancer (7)(8)(9)(10). AXIN1 acts as a tumor suppressor, and thus mutations of AXIN1 serve a significant role in carcinogenesis (8,11).…”