title: Integrin alpha 6: a novel therapeutic target in esophageal squamous cell carcinoma.
abstract: Esophageal squamous cell carcinoma (ESCC), the most common subtype of esophageal cancer in East Asian countries, is a devastating disease characterized by distinctly high incidence and mortality rates. Our previous expression profile analysis showed that integrin alpha 6 (ITGA6) is highly expressed in ESCC tissues. To validate cell surface expression of ITGA6 as a novel target in ESCC, we investigated ITGA6 expression in tumor tissue samples and cell lines of ESCC and found that ITGA6 was upregulated in these cells. In vitro knockdown of ITGA6 in ESCC cells resulted in inhibition of cell proliferation, invasion and colony formation. In addition, we demonstrated that ITGA6 associates with integrin beta 4 (ITGB4), and that this heterodimer complex is upregulated in both ESCC tissues and cell lines. Moreover, our biodistribution results in an ESCC xenograft model indicated that ITGA6 is a possible target for antibody-related diagnostic and therapeutic modalities in ESCC. Thus, our findings suggest that ITGA6 plays an important role in tumorigenesis in ESCC and represents a potential therapeutic target in the treatment of ESCC.
authors.affiliation: Department of Translational Research, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
authors.forename: Junhye
authors.initials: J
authors.lastname: Kwon
authors.forename: Tae-Sup
authors.initials: TS
authors.lastname: Lee
authors.forename: Hae Won
authors.initials: HW
authors.lastname: Lee
authors.forename: Moon Chul
authors.initials: MC
authors.lastname: Kang
authors.forename: Hyeon-Joon
authors.initials: HJ
authors.lastname: Yoon
authors.forename: Ji-Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Jong Ho
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D039503:Integrin alpha6 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D039663:Integrin beta4 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D058990:Molecular Targeted Therapy; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
chemical_list: C059834:ITGB4 protein, human; D039503:Integrin alpha6; D039663:Integrin beta4; D012333:RNA, Messenger; D034741:RNA, Small Interfering