Liu, Tengfei; Yu, Junming; Ge, Chao; Zhao, Fangyu; Chen, Jing; Miao, Chunxiao; Jin, Wenjiao; Zhou, Qingqing; Geng, Qin; Lin, Hechun; Tian, Hua; Chen, Taoyang; Xie, Haiyang; Cui, Ying; Yao, Ming; Xiao, Xiuying; Li, Jinjun; Li, Hong published the artcile< Sperm associated antigen 4 promotes SREBP1-mediated de novo lipogenesis via interaction with lamin A/C and contributes to tumor progression in hepatocellular carcinoma>, Reference of 96829-58-2, the main research area is Hepatocellular carcinoma; Lamin A/C; Lipogenesis; SPAG4; SREBP1.
Hepatocellular carcinoma (HCC) is a highly malignant tumor and its progression is associated with altered lipid metabolism in precancerous lesions, such as non-alc. fatty liver disease. Here, we identified sperm associated antigen 4 (SPAG4), and explored its oncogenic role in HCC progression. Database anal. and immunohistochem. indicated increased level of SPAG4 in HCC tissues which was of prognostic value. Gain/loss-of-function experiments showed that SPAG4 exerted oncogenic roles in HCC growth both in vitro and in vivo. RNA sequencing revealed activation of a lipogenic state and SREBP1-mediated pathway following SPAG4 overexpression. Mechanistically, the N-terminal region of SPAG4 bound to lamin A/C, which increased SREBP1 expression, nuclear translocation, and transcriptional activity. Treatment with orlistat, a lipid synthesis inhibitor, reversed SPAG4-mediated oncogenic effects, and its efficacy varied with SPAG4 level. The effect of orlistat was further amplified when combined with sorafenib in tumor xenograft mouse models. Our study provides evidence that SPAG4 mediates HCC progression by affecting lipid metabolism Administration of orlistat combined with sorafenib reverses SPAG4-mediated oncogenesis in HCC cells and ectopic xenograft tumors in mice, suggesting that this pathway represents a potential target for HCC treatment.
Cancer Letters (New York, NY, United States) published new progress about 96829-58-2. 96829-58-2 belongs to class amides-buliding-blocks, and the molecular formula is C29H53NO5, Reference of 96829-58-2.
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