Possible role of nuclear β‐catenin in resistance to preoperative chemoradiotherapy in locally advanced rectal cancer. Issue 2 (22nd May 2017)

• Record Type: Journal Article
• Authors: Takahashi, Hiroyuki; Nakamura, Kie; Usami, Akane; Tsuruta, Tomoko; Hashimura, Miki; Matsumoto, Toshihide; Saegusa, Makoto
• Is Part Of: Histopathology. Volume 71:Issue 2(2017)
• Page Start: 227
• Page End: 237
• Publication Date: 2017-05-22
• Subjects: cancer stem cell -- chemoradiotherapy -- epithelial–mesenchymal transition -- rectal cancer -- β‐catenin; Histology, Pathological -- Periodicals; 611.018
• DOI: 10.1111/his.13227
• Languages: English
• ISSNs: 0309-0167

Abstract

Abstract : 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.