title: Possible role of nuclear β-catenin in resistance to preoperative chemoradiotherapy in locally advanced rectal cancer.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
authors.forename: Kie
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
authors.forename: Akane
authors.initials: A
authors.lastname: Usami
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tsuruta
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Hashimura
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
authors.forename: Makoto
authors.identifier: http://orcid.org/0000-0001-5366-7149
authors.initials: M
authors.lastname: Saegusa
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D059186:Chemoradiotherapy, Adjuvant; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D020360:Neoadjuvant Therapy; D012004:Rectal Neoplasms / Q000473:pathology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D051176:beta Catenin
keywords: cancer stem cell; chemoradiotherapy; epithelial-mesenchymal transition; rectal cancer; β-catenin