Chiang Yi-Fen, Huang Ko-Chieh, Chen Hsin-Yuan, Huang Tsui-Chin, Ali Mohamed, Chang Hsin-Yi, Shieh Tzong-Ming, Shih Yin-Hwa, Wang Kai-Lee, Huang Yun-Ju, Chung Cheng-Pei, Hsia Shih-Min
School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 110301, Taiwan.
Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110301, Taiwan.
Biomedicines. 2023 Jan 20;11(2):297. doi: 10.3390/biomedicines11020297.
Obesity is a cancer progression risk factor; excessive adipocytes increase adipokine secretion. Visfatin, a novel adipokine highly expressed in cancer patients, is related to breast cancer risk. The modulation of nicotinamide adenine dinucleotide (NAD+) metabolism and the induction of a tumorigenic environment plays a vital role in cancer progression. Among cancer cell types, cancer stem-like cells (CSCs) with self-renewal and chemotherapy-resistance abilities could modulate tumor progression and cancer recurrence ability. In this study, we focused on visfatin's modulation effect on stemness-related properties using the high-malignancy breast cancer cell line MDA-MB-231 in in vitro and in vivo studies. Visfatin treatment significantly increased both the sphere number and sphere diameter and increased the protein expression of NANOG homeobox (NANOG), sex-determining region Y-box 2 (SOX2), and octamer-binding transcription factor 4 (OCT4), as well as SIRT1 protein levels. The serum angiogenesis marker VEGF and extracellular nicotinamide phosphoribosyl transferase (NAMPT, visfatin) were induced after visfatin treatment, increasing the stemness and angiogenesis environment, which were significantly reduced by the visfatin inhibitor FK866. Our results demonstrate that the visfatin-activated SIRT-SOX2 axis promotes triple-negative breast cancer stemness and enriches the tumorigenic microenvironment.
肥胖是癌症进展的风险因素；过多的脂肪细胞会增加脂肪因子的分泌。内脂素是一种在癌症患者中高表达的新型脂肪因子，与乳腺癌风险相关。烟酰胺腺嘌呤二核苷酸（NAD+）代谢的调节和致瘤环境的诱导在癌症进展中起着至关重要的作用。在癌细胞类型中，具有自我更新和化疗抗性能力的癌症干细胞样细胞（CSCs）可以调节肿瘤进展和癌症复发能力。在本研究中，我们在体外和体内研究中，使用高恶性乳腺癌细胞系MDA-MB-231，重点研究了内脂素对干性相关特性的调节作用。内脂素处理显著增加了球体数量和球体直径，并增加了NANOG同源盒（NANOG）、性别决定区Y盒2（SOX2）和八聚体结合转录因子4（OCT4）的蛋白表达，以及SIRT1蛋白水平。内脂素处理后诱导了血清血管生成标志物血管内皮生长因子（VEGF）和细胞外烟酰胺磷酸核糖转移酶（NAMPT，内脂素），增加了干性和血管生成环境，而内脂素抑制剂FK866显著降低了这些指标。我们的结果表明，内脂素激活的SIRT-SOX2轴促进三阴性乳腺癌干性并丰富致瘤微环境。
