Nuclear Receptor SHP as a Potential Therapeutic Target for Liver Cancer

Jenny      Hatch; Shiguo      Liu; Timothy      Gayowski; John      Sorensen; Li      Wang

Abstract

Small heterodimer partner (SHP, NR0B2) is a nuclear receptor that exerts influence over the expression of several nuclear receptors and transcription factors. We have previously shown that SHP is involved in several metabolic and cellular processes. Of particular interest, SHP appears to play a crucial role as a tumor suppressor. We have recently published work demonstrating that SHP knockout (SHP-/-) mice spontaneously develop hepatocellular carcinoma. We have discovered that SHP is a potent inhibitor of cellular proliferation, and that activation of SHP induces apoptosis and inhibits tumor growth. In collateral studies, we have also found that SHP is a key regulator of microRNA gene transcription and through this process can activate apoptosis. Furthermore, we have also shown that SHP expression can be influenced by the degree of methylation. The ability to modulate key cellular processes, particularly cellular proliferation and apoptosis, has heightened interest in the ability of this protein to function as a therapeutic target in hepatomas, as well as other neoplasms. Future research will also examine the sensitivity and specificity of SHP to function as a biomarker for hepatocellular carcinoma.

Keywords: Nuclear receptor, gene transcription, cell cycle, apoptosis, liver cancer.

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