Impact of Aberrant β-Catenin Pathway on Cholangiocarcinoma Heterogeneity

Abstract

The poor prognosis of most cases of advanced cholangiocarcinoma (CCA) constitutes a severe problem in modern oncology, which is aggravated by the fact that the incidence of this liver cancer is increasing worldwide and is often diagnosed late, when surgical removal is not feasible. The difficulty of dealing with this deadly tumor is augmented by the heterogeneity of CCA subtypes and the complexity of mechanisms involved in enhanced proliferation, apoptosis avoidance, chemoresistance, invasiveness, and metastasis that characterize CCA. Among the regulatory processes implicated in developing these malignant traits, the Wnt/β-catenin pathway plays a pivotal role. Alteration of β-catenin expression and subcellular localization has been associated with worse outcomes in some CCA subtypes. This heterogeneity, which also affects cellular and in vivo models commonly used to study CCA biology and anticancer drug development, must be taken into account for CCA investigation to more accurately extrapolate basic laboratory research to the clinical situation. A better understanding of the altered Wnt/β-catenin pathway in relationship with the heterogeneous forms of CCA is mandatory for developing novel diagnostic tools and therapeutic strategies for patients suffering from this lethal disease.

Aberrant β-Catenin Expression and Its Association With Epithelial-Mesenchymal Transition and Clinical Outcomes of Colorectal Cancer

“…Our findings demonstrate that a substantial proportion of CRC tumor samples exhibited aberrant β-catenin expression, (82.3%), while a smaller subset of samples displayed membranous β-catenin expression (11.4%). This observation is consistent with previous studies that have highlighted the prominent role of nuclear β-catenin in CRC [ 13 ]. The observed diversity in β-catenin localization suggests heterogeneity within CRC tumors, possibly reflecting different stages of tumor progression and distinct biological behaviors.…”

Naked cuticle homolog 1 prevents mouse pulmonary arterial hypertension via inhibition of Wnt/β-catenin and oxidative stress

“…Nevertheless, whether NKD1 is also involved in the proliferation and migration of PASMCs remains unrevealed. β-catenin serves as the critical regulator of Wnt signaling pathway and plays an important role in adherens junctions and stabilizing cell-cell contacts [17]. It is demonstrated that increased expression of β-catenin is associated with enhanced proliferation, migration of PASMCs [18], an also accelerated development of PAH [19].…”