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Title: Role of protein misfolding pathway in HBX-induced hepatocellular carcinoma (HCC)
Authors: TAN SU YIN
Keywords: HBX, N-CoR, HCC, protein misfolding, ER stress, Autophagy
Issue Date: 17-Aug-2011
Citation: TAN SU YIN (2011-08-17). Role of protein misfolding pathway in HBX-induced hepatocellular carcinoma (HCC). ScholarBank@NUS Repository.
Abstract: Transcriptional control imparted by nuclear receptor co-repressor (N-CoR) plays an important role in the growth suppressive function of several tumour suppressor proteins. Abrogation of this transcriptional control due to a misfolded conformation dependent loss (MCDL) of N-CoR has been implicated in acute promyelocytic leukemia (APL). It was hypothesized that an APL like MCDL of N- CoR might be involved in other malignancy. Indeed, the initial screening of N-CoR status in various liver cancer (HCC) cell lines revealed an APL like MCDL of N-CoR protein. The N-CoR protein presented in these HCC cells was misfolded and was linked to the amplification of endoplasmic reticulum (ER) stress and cytoprotective unfolded protein response (UPR). siRNA-induced N-CoR ablation led to selective reduction of intracellular ATP level and significantly compromised the growth of HCC cells, suggesting an important role of energy, possibly derived from N-CoR catabolism, in HCC cell growth. These findings identify an important role of autophagy-induced recycling of misfolded N-CoR protein in the selective activation of autonomous survival and growth in HCC cells.
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