Capture-based next-generation sequencing was performed, and alterations in WNT pathway genes (CTNNB1, APC, AXIN1) were seen in 81% of cases (10/13 atypical hepatocellular neoplasms and 12/14 of hepatocellular carcinomas), while the molecular basis of diffuse glutamine synthetase staining was unclear in the remaining 19% of cases.
Although both isoforms are similarly regulated by RUNX1 in estrogen-stimulated ER<sup>+</sup> breast cancer cells, the higher v2/v1 ratio in ER<sup>-</sup> disease is expected to weaken the tumor suppressor activity of AXIN1 in these tumors.
The AXIN1rs1805105 T>C SNP was associated with small tumor size and early tumor stage and the WNT2 rs39315 G allele was associated with advanced tumor stage in HCC.
At the molecular level, SEN461 treatment enhanced the stability of the scaffold protein Axin1, a key negative regulator of the Wnt signaling with tumor suppressor function, resulting in downstream effects coherent with inhibition of canonical Wnt signaling.
Lung cancer cells with a different methylation status of the Axin gene showed different radiosensitivity, suggesting that the methylation status of the Axin gene may be one important factor to predict radiosensitivity of the tumor.
It was previously unknown whether the level of AXIN protein stabilization by tankyrase inhibition is sufficient to impact tumor growth in the absence of normal APC activity.
Aberrant activation of the Wingless-type mouse mammary tumour virus integration site family (Wnt)/beta-catenin signalling pathway due to mutation of adenomatous polyposis coli (APC), beta-catenin (CTNNB1) or AXIN genes is the most common and initial alteration in sporadic colorectal tumours.
Immunoreactivity for Axin1 was strongly positive in normal stratified squamous epithelium but significantly reduced expression of Axin1 was shown in most of the 44 tumor specimens (35/44), especially in poorly differentiated tumors with metastasis.
In the present study, we did not find AXIN1 gene mutations in 17 GEJ tumours with nuclear beta-catenin expression (without beta-catenin exon 3 mutations).
This accumulation correlates with either mutational activation of CTNNB1 (beta-catenin) or mutational inactivation of APC and Axin1 genes in some tumors.
Our results indicated that mutations of Axin gene as a mechanism of tumorigenesis are not associated with pediatric renal tumors including Wilms' tumors.
In the remaining 29 primary OEAs, unequivocal nuclear beta-catenin immunoreactivity was not observed, though a nonsense mutation in AXIN1 was observed in one tumor and a truncating frameshift mutation in AXIN2 was seen in another case.