Cui Zhu

Publications (2)20.05 Total impact

• Article: Human four-and-a-half LIM family members suppress tumor cell growth through a TGF-beta-like signaling pathway.

  Lihua Ding, Zhaoyun Wang, Jinghua Yan, Xiao Yang, Aijun Liu, Weiyi Qiu, Jianhua Zhu, Juqiang Han, Hao Zhang, Jing Lin, [......], Xi Qin, Chang Niu, Bin Yuan, Xiaohui Wang, Cui Zhu, Yan Zhou, Jiezhi Li, Haifeng Song, Cuifen Huang, Qinong Ye
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  ABSTRACT: The four-and-a-half LIM (FHL) proteins belong to a family of LIM-only proteins that regulate cell proliferation, differentiation, and apoptosis. The exact functions of each FHL protein in cancer development and progression remain unknown. Here we report that FHL1, FHL2, and FHL3 physically and functionally interact with Smad2, Smad3, and Smad4, important regulators of cancer development and progression, in a TGF-beta-independent manner. Casein kinase 1delta, but not the TGF-beta receptor, was required for the FHL-mediated TGF-beta-like responses, including increased phosphorylation of Smad2/3, interaction of Smad2/3 and Smad4, nuclear accumulation of Smad proteins, activation of the tumor suppressor gene p21, and repression of the oncogene c-myc. FHL1-3 inhibited anchorage-dependent and -independent growth of a human hepatoma cell line in vitro and tumor formation in nude mice. Further analysis of clinical samples revealed that FHL proteins are often downregulated in hepatocellular carcinomas and that this correlates with decreased TGF-beta-like responses. By establishing a link between FHL proteins and Smad proteins, this study identifies what we believe to be a novel TGF-beta-like signaling pathway and indicates that FHL proteins may be useful molecular targets for cancer therapy.
  Journal of Clinical Investigation 02/2009; 119(2):349-61. · 15.39 Impact Factor
• Article: The estrogen receptor-interacting protein HPIP increases estrogen-responsive gene expression through activation of MAPK and AKT.

  Xiaohui Wang, Zhihong Yang, Hao Zhang, Lihua Ding, Xiru Li, Cui Zhu, Yiqiong Zheng, Qinong Ye
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  ABSTRACT: Estrogen receptors (ERalpha and ERbeta) are estrogen-regulated transcription factors that play important roles in the development and progression of breast cancer. The biological function of ERs has been shown to be modulated by ER-interacting proteins. However, the ER-interacting proteins that not only activate MAPK and AKT, two important growth regulatory protein kinases, but also increase growth related estrogen-responsive gene expression remain unknown. Here, we report that hematopoietic PBX-interacting protein (HPIP) interacts both with ERalpha and with ERbeta, and increases ERalpha target gene expression through activation of MAPK and AKT and enhanced ERalpha phosphorylation. ERbeta inhibits ERalpha target gene expression, possibly by competition of ERbeta with ERalpha for binding to HPIP, and by a decrease in available ERalpha for HPIP binding through the interaction of ERbeta with ERalpha. Furthermore, HPIP increases breast cancer cell growth. These data suggest that HPIP may be an important regulator in ER signaling and that the relative ratio of ERbeta to ERalpha may be important for HPIP function.
  Biochimica et Biophysica Acta 07/2008; 1783(6):1220-8. · 4.66 Impact Factor