Possible role of nuclear β-catenin in resistance to preoperative chemoradiotherapy in locally advanced rectal cancer.

AIMS: β-Catenin signalling participates in the regulation of epithelial-mesenchymal transition (EMT)/cancer stem cell (CSC) properties. The aim of this study was to investigate the role of β-catenin in resistance to neoadjuvant chemoradiotherapy in patients with rectal cancer, especially pertaining to its association with EMT/CSC features.

METHODS AND RESULTS: A total of 109 cases of locally advanced rectal cancer, along with a colon cancer cell line, were investigated. Nuclear β-catenin accumulation in pretreatment-biopsied samples was inversely associated with the therapeutic efficacy of chemoradiotherapy in resected rectal cancer. In resected tumours, nuclear β-catenin was predominantly observed in EMT-like lesions with decreased E-cadherin and increased Snail expression, along with expression of CSC-related markers. The EMT-like lesions also showed significant decreases in both apoptosis and cell proliferation as compared with non-EMT lesions. In-vitro culture of a colon cancer cell line in STK2 was sufficient to induce EMT/CSC properties together with nuclear β-catenin accumulation, and showed inhibition of cell proliferation and resistance to doxorubicin treatment.

CONCLUSION: Nuclear β-catenin accumulation may contribute to chemoradioresistance in locally advanced rectal cancer, probably through its regulation of EMT/CSC properties. In addition, nuclear β-catenin in pretreatment-biopsied samples is useful in predicting the efficacy of chemoradiotherapy in patients with rectal cancer.