华中科大:大肠癌细胞间的代谢共生如何影响肿瘤生长?
创作:Lexi 审核:Lexi 2020年09月14日
  • 建立结直肠癌(CRC)患者来源类器官,相比肿瘤干细胞(CSCs),非CSCs具有高度糖酵解,且产生更多乳酸;
  • 非CSC来源的乳酸可增强CSCs的氧化磷酸化(OXPHOS)活性,且促进CSCs的自我更新;
  • 单羧酸转运蛋白(MCT,包括MCT1和MCT4)介导非CSCs和CSCs间的穿梭,从而促进小鼠移植瘤生长;
  • OXPHOS来源的ROS通过激活AKT从而促进CSCs中的Wnt/β-连环蛋白信号,该途径可由非CSCs来源的乳酸触发;
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Lexi
肿瘤内包含了具有不同代谢特征和表型的细胞,但不同癌细胞亚群的代谢共生作用如何影响肿瘤进展尚不清楚。来自华中科技大学的Jichao Qin研究团队在Cancer Letters发表的最新研究表明,结直肠癌肿瘤干细胞(CSCs)和非CSCs具有不同的代谢特征,且非CSCs来源的乳酸可促进CSCs自我更新,从而促进肿瘤生长。
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Cancer Letters [IF:7.36]

Differentiated cancer cell-originated lactate promotes the self-renewal of cancer stem cells in patient-derived colorectal cancer organoids

分化的癌细胞来源乳酸盐促进肿瘤干细胞在患者来源结直肠癌类器官zhong的自我更新

10.1016/j.canlet.2020.08.044

2020-09-06, Article

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Tumors harbor diverse compartments of cells with distinct metabolic properties and phenotypes, but the mechanism by which metabolic commensalism among distinct subsets of cancer cells affects tumor progression remains unclear. Colorectal cancer (CRC) has been reported to consist of cancer stem cells (CSCs) and differentiated cancer cells (non-CSCs). In the present study, organoid models were employed to show that CSCs and non-CSCs in CRC were characterized by distinct metabolic phenotypes. Treatment with either non–CSC–derived conditioned medium or exogenous lactate enhanced organoid-forming and tumor-initiating capacity of CSCs. In tumor regeneration assays with co-implanted CSCs and non-CSCs, the tumor-initiating activity was reduced when either monocarboxylate transporter (MCT)4 in non-CSCs or MCT1 in CSCs was silenced or inhibited. Mechanistically, oxiadative phosphorylation-derived reactive oxygen species in CSCs activated AKT-Wnt/β-catenin signaling, which could be induced by lactate from non-CSCs. Overall, these results suggest that CSCs and non-CSCs possess distinct metabolic profiles and, unexpectedly, non–CSC–originated lactate promotes self-renewal of CSCs and thus contributes to CRC progression. Our findings establish a rationale for developing novel therapies targeting the metabolic commensalism between different cell populations in CRC.

First Authors:
Hui Zhao,Chang Yan

Correspondence Authors:
Jichao Qin

All Authors:
Hui Zhao,Chang Yan,Yibing Hu,Lei Mu,Shuang Liu,Kaiyu Huang,Qilin Li,Xiaolan Li,Deding Tao,Jichao Qin

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