title: TGF-β and EGF induced HLA-I downregulation is associated with epithelial-mesenchymal transition (EMT) through upregulation of snail in prostate cancer cells.
abstract: Human leukocyte antigen class I antigens (HLA-I) is essential in immune response by presenting antigenic peptides to cytotoxic T lymphocytes. Downregulation of HLA-I is observed in primary and metastatic prostate cancers, which facilitates them escape from immune surveillance, thereby promotes prostate cancer progression. In addition, elevated level of growth factors like TGF-β or EGF in microenvironment is related to the prostate cancer deterioration. Thus, we wondered whether TGF-β or EGF was involved in the regulation of HLA-I during the development of prostate cancer cells. In this study, we demonstrated that TGF-β and EGF both downregulated the expression of HLA-I, thereby attenuated the cytotoxic T cell mediated lysis of prostate cancer cells. Next, we revealed that TGF-β and EGF induced downregulation of HLA-I is associated with classical epithelial-mesenchymal transition (EMT) morphological changes and expression profiles. We further illustrated that overexpression of Snail is crucial for HLA-I downregulation and its association with EMT. At last, we discussed that NF-κB/p65 is the plausible target for Snail to induce HLA-I downregulation. Taken together, this is the first evidence to reveal that both TGF-β and EGF can induce HLA-I downregulation which is then proven to be associated with EMT in prostate cancer cells. These discoveries provide a deeper understanding of growth factors induced immune escape and introduce potential therapeutic targets for prostate cancers.
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, No. 132 Waihuandong Road, University Town, Guangzhou 510006, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Chen
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, No. 132 Waihuandong Road, University Town, Guangzhou 510006, China.
authors.forename: Zong-Cai
authors.initials: ZC
authors.lastname: Liu
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, No. 132 Waihuandong Road, University Town, Guangzhou 510006, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, No. 132 Waihuandong Road, University Town, Guangzhou 510006, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Jinan University, Guangzhou 510632, PR China.
authors.forename: Xiao-Xiong
authors.initials: XX
authors.lastname: Wang
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, No. 132 Waihuandong Road, University Town, Guangzhou 510006, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, No. 132 Waihuandong Road, University Town, Guangzhou 510006, China.
authors.forename: Hong-Peng
authors.initials: HP
authors.lastname: Ke
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, No. 132 Waihuandong Road, University Town, Guangzhou 510006, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, No. 132 Waihuandong Road, University Town, Guangzhou 510006, China. Electronic address: whongsh@mail.sysu.edu.cn.
authors.forename: Hong-Sheng
authors.initials: HS
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Jinan University, Guangzhou 510632, PR China. Electronic address: csh5689@sina.com.
authors.forename: Shao-Hui
authors.initials: SH
authors.lastname: Cai
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, No. 132 Waihuandong Road, University Town, Guangzhou 510006, China. Electronic address: dujun@mail.sysu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Du
mesh_terms: D045744:Cell Line, Tumor; D015536:Down-Regulation; D004815:Epidermal Growth Factor / Q000096:biosynthesis / Q000276:immunology*; D058750:Epithelial-Mesenchymal Transition / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000276:immunology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D051996:Transcription Factor RelA / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000276:immunology*; D019139:Tumor Escape / Q000276:immunology; D015854:Up-Regulation
chemical_list: D015395:Histocompatibility Antigens Class I; C498143:RELA protein, human; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; D051996:Transcription Factor RelA; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor
keywords: Epithelial-mesenchymal transition (EMT); HLA-I; Immune escape; Prostate cancer; Snail