title: p63-Mediated activation of the β-catenin/c-Myc signaling pathway stimulates esophageal squamous carcinoma cell invasion and metastasis.
abstract: The development of esophageal squamous carcinomas (ESC) results from numerous genetic alterations. Our previous study demonstrated that p63 is highly expressed in human ESC cells and stimulates their growth; however, the mechanism by which p63 regulates ESC cell adhesion and invasion remains unclear. In the present study, we further elucidated the underlying molecular mechanisms by which p63 regulates metastasis in ESC cells. Knockdown of p63 significantly diminished the invasion of ESC cell lines TE-8 and TE-12, whereas overexpression of p63 significantly increased the migration rates of BE3 and OE33 cells. The mRNA and protein levels of vimentin, twist, SUSD2, and uPA were significantly decreased in p63-knockdown ESC cells, while overexpression of p63 induced an increase in vimentin, SUSD2, and uPA. In addition, knockdown of p63 in ESC cells significantly reduced levels of β-catenin and c-Myc, while overexpression of p63 increased β-catenin, but reduced p-β-catenin level. Therefore, p63 regulates the migration and invasion of ESC cells through activation of the β-catenin/c-Myc pathway. Our results suggest that targeting p63 may constitute a potential therapeutic strategy for ESC.
authors.affiliation: Department of Orthopedic Surgery, Chonbuk National University Medical School and Hospital, Jeonju 561-181, Republic of Korea.
authors.forename: Kwang Bok
authors.initials: KB
authors.lastname: Lee
authors.affiliation: Department of Orthopedic Surgery, Chonbuk National University Medical School and Hospital, Jeonju 561-181, Republic of Korea.
authors.forename: Shuai
authors.initials: S
authors.lastname: Ye
authors.affiliation: Catholic University of Pusan, Busan 609-757, Republic of Korea.
authors.forename: Man Hee
authors.initials: MH
authors.lastname: Park
authors.affiliation: Department of Biochemistry, Chonbuk National University Medical School, Jeonju 561-181, Republic of Korea.
authors.forename: Byung Hyun
authors.initials: BH
authors.lastname: Park
authors.affiliation: Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, USA.
authors.forename: Ju-Seog
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Physiology, Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju 561-181, Republic of Korea. Electronic address: soomikim@jbnu.ac.kr.
authors.forename: Soo Mi
authors.initials: SM
authors.lastname: Kim
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D014746:Vimentin / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; C489427:MYC protein, human; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; C582626:SUSD2 protein, human; C115051:TP63 protein, human; C103173:TWIST1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D051879:Twist-Related Protein 1; D014746:Vimentin; D051176:beta Catenin; D014568:Urokinase-Type Plasminogen Activator
keywords: Esophageal squamous carcinoma cell; Twist; c-Myc; p63; β-catenin