发现乳腺癌肺转移和骨转移发生中的关键定植分子和微环境中关键促癌基质细胞

郑撼球教授目前的研究重点是肿瘤细胞和肿瘤微环境的互作对癌症发生、转移和耐药的作用。癌症已经在很多国家成为导致病人死亡的第一大疾病。癌症发生远端组织转移和耐药发生是导致病人死亡的主要原因。而肿瘤的微环境(肿瘤周围的正常组织结构和组织细胞)对癌症的转移和耐药性有重大影响。因而，了解转移肿瘤微环境和耐药的关键分子机制对了解癌症发生机理和发现治疗新靶点有重要价值。郑撼球实验室通过利用先进的小鼠模型，生物信息学分析，和经典细胞和分子生物学，期望揭示肿瘤细胞－组织细胞相互作用在癌症转移（特别是骨转移）和耐药性中的重要功能。这些发现的新机制可以帮助设计更有效的癌症治疗手段去抑制癌症转移和减小癌症耐药性。

郑撼球团队通过开发一套双荧光素标记系统，鉴定出了促进癌症转移的重要转录因子SNAIL的E3泛素连接酶FBXO11（Cancer Cell, 2014），该系统已得到国际同行的认可和使用；此外，他研究了Notch信号通路重要配体Jagged 1在癌症骨转移中的功能，发现JAGGED1促进乳腺癌骨转移的早期定植，并帮助骨转移癌细胞化疗耐药性发生，在此基础上，开发了针对JAGGED1的人源化抗体 （Cancer Cell，2017）。郑撼球教授参与了另外两项关于癌症分泌因子等参与转移定植课题的研究，相关结果陆续发表在癌症细胞生物学领域顶级期刊（Cancer Cell，2019； Nature Cell Biology, 2019）。实验室目前在乳腺癌骨转移的早期定植信号分析、耐药发生机制等方面有大量的细胞模型、小鼠模型及技术分析方法的积累。

1.Fan H.; Wang X.; Li W.; Shen M.; Wei Y.;Zheng H.*;Kang Y.*; ASB13 inhibits breast cancer metastasis through promoting SNAI2 degradation and relieving its transcriptional repression of YAP,Genes & Development, 2020, 34(19-20): 1359-1372

2.LiW.; ShenM.; JiangY.Z.; ZhangR.;ZhengH.;Wei Y.;Shao Z.M.;KangY.*; Deubiquitinase USP20 promotes breast cancer metastasis by stabilizing SNAI2,Genes&Development,2020, 34(19-20): 1310-1315

3.Esposito M*,MondalN, Greco TM, Yong W, Spadazzi C, Lin SC,Zheng H, Cheung C, Magnani JL, Lin SH, Cristea IM,SacksteinR, Kang Y^#(2019) Bone vascular niche E-selectin induces mesenchymal–epithelial transition and Wnt activation in cancer cells to promote bone metastasisNature Cell Biology, 21(5): 627-639 PMID: 30988423

4.Shen M*, Jiang YZ, Wei Y, Ell B, Sheng X, Esposito M, Kang J, Hang X,Zheng H, Rowicki M, Zhang L, Shih WJ, Celià-Terrassa T, Liu Y, Cristea I, Shao ZM, Yibin Kang^#(2019) Tinagl1 suppresses triple-negative breast cancer progression and metastasis by simultaneously inhibiting integrin/FAK and EGFR signalingCancer Cell, 35(1): 64-80.e7 PMID: 30612941

5.Zheng H*, Bae Y*, Kasimir-bauer S, Tang R, Chen J, Ren G, Yuan M, Esposito M, Li W, Wei Y, Shen M, Zhang L, Tupitsyn N, Pantel K, King C, Sun J, Moriguchi J, Jun HT, Coxon A,Lee B^#, Kang Y^#(2017) Therapeutic Antibody Targeting Tumor- and Osteoblastic Niche-Derived Jagged1 Sensitizes Bone Metastasis to ChemotherapyCancer Cell, 32(6): 731-47 e6 PMID: 29232552

6.Zheng H, Li W, and Kang Y. (2017)Tumor –Stroma Interactions in Bone Metastasis: Molecular Mechanisms and Therapeutic Implications.Cold Spring Harb. Symp. Quant. Biol., doi: 10.1101/sqb.2016.81.030775

7.Zheng H & Kang Y (2015)Cradle of evil: osteogenic niche forearlybone metastasisCancer Cell27(2): 153-5. PMID: 25670074

8.Zheng H, Shen M, Cha Y-L, Li W, Wei Y, Blanco MA, Ren G, Zhou T, Storz P, Wang H-Y, and Kang Y. (2014) PKD1 phosphorylation-dependent degradation of SNAIL by SCF-FBXO11 regulates epithelial-mesenchymal transition and metastasis.Cancer Cell, 26(3): 358-73. PMID: 25203322

9.Zheng, H& Kang, Y. (2014) Multilayer control of the EMT master regulators.Oncogene33, 1755-1763. PMID: 23604123

10.Zhao D*,Zheng HQ*, Zhou Z, and Chen C(2010)The Fbw7 tumor suppressor targets KLF5 for ubiquitin-mediated degradation and suppresses breast cell proliferation.Cancer Res., 70(11):4728-38. PMID: 20484041

11.Liu R,Zheng HQ, Zhou Z, Dong JT, and Chen C (2009) KLF5 promotes breast cell survival partially through FGF-BP-pERK-mediated MKP-1 protein phosphorylation and stabilization.J Biol. Chem., 284(25):16791-8. PMID: 19668233

12.Zheng HQ, Zhou Z, Huang J, Chaudhury L, Dong JT, and Chen C (2009) Kruppel-Like Factor 5 Promotes Breast Cell Proliferation Partially through Upregulating the Transcription of Fibroblast Growth Factor-Binding Protein 1.Oncogene, 28(42):3702-13. PMID: 19411256（其他信息）

学术荣誉与奖励

2018 中国国家人才计划青年项目

2018 拜耳清华研究员奖

开设课程

肿瘤生物学

肿瘤生物学概论

医学细胞生物学

专利技术

Patent application: Yibin Kang,Hanqiu Zheng: Methods of treating or preventing breast cancer metastases using antibodies to jagged1 and chemotherapeutic agents