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Title: Thymosin β4 induces invasion and migration of human colorectal cancer cells through the ILK/AKT/β-catenin signaling pathway

Highlights: • Tβ4 is overexpressed in human colorectal cancer cells. • The overexpression of Tβ4 is correlated with stage of colorectal cancer. • Tβ4 stimulates cell adhesion, invasion, migration and EMT. • Tβ4 activates the ILK/AKT/β-catenin signaling pathway. - Abstract: Thymosin β4 (Tβ4) is a 43-amino-acid peptide involved in many biological processes. However, the precise molecular signaling mechanism(s) of Tβ4 in cell invasion and migration remain unclear. In this study, we show that Tβ4 was significantly overexpressed in colorectal cancer tissues compared to adjacent normal tissues and high levels of Tβ4 were correlated with stage of colorectal cancer, and that Tβ4 expression was associated with morphogenesis and EMT. Tβ4-upregulated cancer cells showed increased adhesion, invasion and migration activity, whereas Tβ4-downregulated cells showed decreased activities. We also demonstrated that Tβ4 interacts with ILK, which promoted the phosphorylation and activation of AKT, the phosphorylation and inactivation of GSK3β, the expression and nuclear localization of β-catenin, and integrin receptor activation. These results suggest that Tβ4 is an important regulator of the ILK/AKT/β-catenin/Integrin signaling cascade to induce cell invasion and migration in colorectal cancer cells, and is a potential target for cancer treatment.
Authors:
 [1] ;  [2] ;  [1] ;  [3] ;  [4] ;  [1] ;  [2] ;  [5]
  1. Research Center for Molecular Therapeutic to GI Tract of Cancer Center, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of)
  2. (BK-21 Plus Project), Chonnam National University Medical School, Gwangju (Korea, Republic of)
  3. Department of Gastroenterologic Surgery, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of)
  4. Department of Pathology, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of)
  5. (Korea, Republic of)
Publication Date:
OSTI Identifier:
22416763
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 452; Journal Issue: 3; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADHESION; AMINO ACIDS; ANIMAL TISSUES; COMPARATIVE EVALUATIONS; HUMAN POPULATIONS; INACTIVATION; MIGRATION; MORPHOGENESIS; NEOPLASMS; PEPTIDES; PHOSPHORYLATION; RECEPTORS; TUMOR CELLS