Program of Immunology and Tumor Biology, Brazilian National Cancer Institute (INCA), Rio de Janeiro, RJ, Brazil.
Program of Molecular Carcinogenesis, Brazilian National Cancer Institute (INCA), Rio de Janeiro, RJ, Brazil.
Mol Cell Biol. 2019 Apr 16;39(9). doi: 10.1128/MCB.00374-18. Print 2019 May 1.
Intracellular lipid accumulation has been associated with a poor prognosis in cancer. We have previously reported the involvement of lipid droplets in cell proliferation in colon cancer cells, suggesting a role for these organelles in cancer development. In this study, we evaluate the role of lipid droplets in cell cycle regulation and cellular transformation. Cell cycle synchronization of NIH 3T3 cells revealed increased numbers and dispersed distribution of lipid droplets specifically during S phase. Also, the transformed cell lineage NIH 3T3-H- showed an accumulation of both lipid droplets and PLIN2 protein above the levels in NIH 3T3 cells. gene overexpression, however, was not able to induce NIH 3T3 cell transformation, disproving the hypothesis that is an oncogene. Furthermore, positive PLIN2 staining was strongly associated with highly proliferative Ki-67-positive areas in human colon adenocarcinoma tissue samples. Taken together, these results indicate that cell cycle progression is associated with tight regulation of lipid droplets, a process that is altered in transformed cells, suggesting the existence of a mechanism that connects cell cycle progression and cell proliferation with lipid accumulation.
细胞内脂质积累与癌症预后不良有关。我们之前曾报道过脂滴参与结肠癌细胞的增殖,这表明这些细胞器在癌症发展中起作用。在这项研究中,我们评估了脂滴在细胞周期调控和细胞转化中的作用。NIH 3T3 细胞的细胞周期同步化显示,脂质滴的数量增加,并且在 S 期特别分散。此外,转化细胞系 NIH 3T3-H-显示脂质滴和 PLIN2 蛋白的积累水平高于 NIH 3T3 细胞。然而,基因过表达未能诱导 NIH 3T3 细胞转化,从而否定了基因是致癌基因的假设。此外,PLIN2 的阳性染色与人类结肠腺癌组织样本中高度增殖的 Ki-67 阳性区域强烈相关。总之,这些结果表明细胞周期进展与脂质滴的紧密调节有关,这一过程在转化细胞中发生改变,表明存在一种将细胞周期进展和细胞增殖与脂质积累联系起来的机制。