title: LGR5 expression is controled by IKKα in basal cell carcinoma through activating STAT3 signaling pathway.
abstract: Basal cell carcinomas (BCC) of the skin are the most common of human cancers. The noncanonical NF-κB pathway is dependent on IKKα. However, the role of IKKα in BCC has not been elucidated. We show here that IKKα is expressed in the nucleus in BCC and non-malignant diseases. Nuclear IKKα could directly bind to the promoters of inflammation factors and LGR5, a stem cell marker, in turn, upregulating LGR5 expression through activation of STAT3 signaling pathway during cancer progression. Activation of STAT3 signaling pathway contributes LGR5 expression in dependent of IKKα after the interplay between STAT3 and IKKα. Meanwhile knockdown of IKKα inhibits tumor growth and transition of epithelial stage to mescheme stage. Taken together, we demonstrate that IKKα functions as a bone fide chromatin regulator in BCC, whose promoted expression contributes to oncogenic transformation via promoting expression stemness- and inflammatory- related genes. Our finding reveals a novel viewpoint for how IKKα may involve in BCCs tumor progression in the inflammatory microenvironment.
authors.affiliation: Center for Medicine Research, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Cancer Research Institute, Central South University, Changsha, Hunan, China.|Pathophysiology Department of Changzhi Medical College, Changzhi, Shanxi, China.
authors.forename: Jiantao
authors.initials: J
authors.lastname: Jia
authors.affiliation: Cancer Research Institute, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, China.|Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Cancer Research Institute, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, China.|Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yan
authors.affiliation: Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Deshen
authors.initials: D
authors.lastname: Xiao
authors.affiliation: Cancer Research Institute, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, China.|Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Lai
authors.affiliation: Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Cancer Research Institute, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, China.|Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, China.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Cancer Research Institute, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, China.|Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Cancer Research Institute, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, China.|Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Mao
authors.affiliation: Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, China.|Institute of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Thoracic Surgery Section, Thoracic and GI Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Sichuan
authors.initials: S
authors.lastname: Xi
authors.affiliation: Cancer Research Institute, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, China.|Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Center for Medicine Research, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Center for Medicine Research, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Cancer Research Institute, Central South University, Changsha, Hunan, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, China.|Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, China.
authors.forename: Yongguang
authors.initials: Y
authors.lastname: Tao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002280:Basal Cell Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D008819:Mice, Nude; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014183:Transplantation, Heterologous
chemical_list: C116884:LGR5 protein, human; D043562:Receptors, G-Protein-Coupled; D050796:STAT3 Transcription Factor; D051550:I-kappa B Kinase
keywords: BCC; EGF; IKKα; LGR5; STAT3