title: Thymosin β4 induces invasion and migration of human colorectal cancer cells through 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.affiliation: Research Center for Molecular Therapeutic to GI Tract of Cancer Center, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea; Center for Creative Biomedical Scientists (BK-21 Plus Project), Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Zhengri
authors.initials: Z
authors.lastname: Piao
authors.affiliation: Research Center for Molecular Therapeutic to GI Tract of Cancer Center, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea.
authors.forename: Chang-Soo
authors.initials: CS
authors.lastname: Hong
authors.affiliation: Department of Gastroenterologic Surgery, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea.
authors.forename: Mi-Ran
authors.initials: MR
authors.lastname: Jung
authors.affiliation: Department of Pathology, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea.
authors.forename: Chan
authors.initials: C
authors.lastname: Choi
authors.affiliation: Research Center for Molecular Therapeutic to GI Tract of Cancer Center, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea; Center for Creative Biomedical Scientists (BK-21 Plus Project), Chonnam National University Medical School, Gwangju, Republic of Korea; Department of Gastroenterologic Surgery, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea. Electronic address: parkyk@jnu.ac.kr.
authors.forename: Young-Kyu
authors.initials: YK
authors.lastname: Park
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013947:Thymosin / Q000235:genetics* / Q000378:metabolism; D059016:Tumor Microenvironment; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism; D000099201:Thymosin beta(4); D000099200:Scaffold Protein ILK
chemical_list: D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D016023:Integrins; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D013947:Thymosin; D051176:beta Catenin; D000099201:Thymosin beta(4); D000099200:Scaffold Protein ILK; C495270:CTNNB1 protein, human; C000605506:GSK3B protein, human
keywords: Adhesion; Colorectal cancer; Invasion; Migration; Thymosin β4