从HK1到TGF-β1的一个独特的细胞间料循环促进肝细胞癌的进展
Qi-Tao Chen1, Qiao-Ling Huang1, De-Yi Feng1
1State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
肝细胞癌 (HCC) 细胞促进葡萄糖新陈代谢,通过细胞外膀hexokinase 1 (EV HK1) 激活肝星细胞 (HSC). 这创造了一个亲瘤源循环,推动HCC的进展,但破坏它会抑制瘤的生长.
科学领域:
- 肝细胞癌 (HCC) 研究研究
- 肝纤维化机制 肝纤维化机制
- 癌细胞的新陈代谢
背景情况:
- 肝细胞癌 (HCC) 在纤维化的肝脏环境中发展.
- 肝星细胞 (HSC) 是肝纤维化的关键驱动因素.
- HCC细胞和HSC之间的细胞间通信会影响瘤的进展.
研究的目的:
- 为了研究HCC细胞和HSC之间的相互激活.
- 为了阐明细胞外囊泡hexokinase 1 (EV HK1) 在这种交叉中所扮演的角色.
- 探索针对这种通信循环的治疗策略,以治疗HCC.
主要方法:
- 对HCC细胞和HSC共同培养的分析.
- 大型细胞外囊泡 (lEVs) 及其载荷的表征.
- 代谢途径分析,包括六胺生物合成途径.
- 在体内小鼠模型的HCC进展.
- 对针对细胞间通信的治疗干预措施的评估.
主要成果:
- 增强葡萄糖代谢的HCC细胞相互激活HSCs.
- 由HSCs分泌的lEV HK1增强了HCC细胞激活HSCs的能力.
- HK1促进转化成长因子β1 (TGF-β1) 的N-糖化,促进其分泌和随后的HSC激活.
- 在HCC细胞和HCC之间有一个前循环,加剧了HCC的进展.
- 在小鼠模型中,这种通信的中断显著抑制了HCC的进展.
结论:
- 一个涉及lEV HK1的新型前循环介导了HCC细胞和HSC之间的交叉声.
- 这种循环促进了前瘤纤维化微环境,并推动了HCC的进展.
- 针对这种细胞间通信是HCC的有希望的治疗策略.
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