BRD4 inhibitor suppresses melanoma metastasis via the SPINK6/EGFR-EphA2 pathway

作者全名："Hu, Rui; Li, Yao; Guo, Ying; Li, Xin; Du, Songtao; Liao, Mengting; Hou, Huihui; Sun, Hongyin; Zhao, Shuang; Su, Juan; Chen, Xiang; Yin, Mingzhu"

作者地址："[Hu, Rui; Guo, Ying; Li, Xin; Du, Songtao; Liao, Mengting; Hou, Huihui; Sun, Hongyin; Zhao, Shuang; Su, Juan; Chen, Xiang; Yin, Mingzhu] Cent South Univ, Xiangya Hosp, Hunan Engn Res Ctr Skin Hlth & Dis, Hunan Key Lab Skin Canc & Psoriasis,Dept Dermatol, Changsha 410008, Hunan, Peoples R China; [Hu, Rui] Chongqing Med Univ, Affiliated Hosp 1, Dept Dermatol, Chongqing, Peoples R China; [Hu, Rui; Guo, Ying; Li, Xin; Du, Songtao; Liao, Mengting; Hou, Huihui; Sun, Hongyin; Zhao, Shuang; Su, Juan; Chen, Xiang; Yin, Mingzhu] Cent South Univ, Natl Engn Res Ctr Personalized Diagnost & Therapeu, Changsha 410008, Hunan, Peoples R China; [Li, Yao] Yale Sch Med, Dept Pathol, New Haven, CT 06520 USA; [Liao, Mengting] Cent South Univ, Hlth Management Xiangya Hosp, Changsha 410008, Hunan, Peoples R China"

通信作者："Chen, X; Yin, MZ (通讯作者)，Cent South Univ, Xiangya Hosp, Hunan Engn Res Ctr Skin Hlth & Dis, Hunan Key Lab Skin Canc & Psoriasis,Dept Dermatol, Changsha 410008, Hunan, Peoples R China."

来源：PHARMACOLOGICAL RESEARCH

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000964691400001

JCR分区：Q1

影响因子：9.1

年份：2023

卷号：187

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Melanoma; BET inhibitor; BRD4; SPINK6; EphA2; EGFR

摘要："BET inhibition or BRD4 depletion is a promising and attractive therapy for metastatic melanoma; however, the mechanism is still unclear. Here, we indicated that BET inhibition suppressed melanoma metastasis both in vitro and in vivo and identified a new mechanism by which BET inhibitors suppress melanoma metastasis by blocking the direct interaction of BRD4 and the SPINK6 enhancer. Moreover, we demonstrated that SPINK6 activated the EGFR/EphA2 complex in melanoma and the downstream ERK1/2 and AKT pathways. Thus, these results identified the SPINK6/EGFR-EphA2 axis as a new oncogenic pathway in melanoma metastasis and support the further development of BRD4 inhibitors for the treatment of metastatic melanoma in the clinic."

基金机构："General Program, The National Natural Science Foundation of China [81874138, 82073020]; Hunan Natural Science Foundation for Distinguished Young Scholars [2021JJ10073]; China Postdoctoral Science Foundation [2021M693559]; Natural Science Foundation of Hunan Province [2021JJ41004]"

基金资助正文："This study was supported by grants from General Program, The National Natural Science Foundation of China (No. 81874138 and 82073020) , Hunan Natural Science Foundation for Distinguished Young Scholars (No.2021JJ10073) , China Postdoctoral Science Foundation (No.2021M693559) , and The Natural Science Foundation of Hunan Province (No.2021JJ41004) ."