创作:爱的抉择 审核:szx 2019年12月30日
  • ATP合成酶抑制剂1(IF1)在多种肿瘤高表达,促进代谢重编程和癌症进展;
  • 然而在结直肠癌患者中,IF1的高表达与较低的复发率、较高的总生存期及无病生存期相关;
  • 与高表达IF1的结肠癌细胞相比,IF1敲低导致细胞具有更强的侵入性、致瘤潜能及转移潜能;
  • 机制上,IF1敲低导致cFLIP介导的对细胞失巢凋亡的抵抗增加,以增强癌症细胞的转移潜能;
  • IF1敲低的细胞形成肿瘤球状体,促进其逃避NK细胞的免疫监视。
Cancers [IF:6.126]

Overexpression of Mitochondrial IF1 Prevents Metastatic Disease of Colorectal Cancer by Enhancing Anoikis and Tumor Infiltration of NK Cells



2019-12-19, Article

Abstract & Authors:展开

Increasing evidences show that the ATPase Inhibitory Factor 1 (IF1), the physiological inhibitor of the ATP synthase, is overexpressed in a large number of carcinomas contributing to metabolic reprogramming and cancer progression. Herein, we show that in contrast to the findings in other carcinomas, the overexpression of IF1 in a cohort of colorectal carcinomas (CRC) predicts less chances of disease recurrence, IF1 being an independent predictor of survival. Bioinformatic and gene expression analyses of the transcriptome of colon cancer cells with differential expression of IF1 indicate that cells overexpressing IF1 display a less aggressive behavior than IF1 silenced (shIF1) cells. Proteomic and functional in vitro migration and invasion assays confirmed the higher tumorigenic potential of shIF1 cells. Moreover, shIF1 cells have increased in vivo metastatic potential. The higher metastatic potential of shIF1 cells relies on increased cFLIP-mediated resistance to undergo anoikis after cell detachment. Furthermore, tumor spheroids of shIF1 cells have an increased ability to escape from immune surveillance by NK cells. Altogether, the results reveal that the overexpression of IF1 acts as a tumor suppressor in CRC with an important anti-metastatic role, thus supporting IF1 as a potential therapeutic target in CRC.

First Authors:
Lucía González-Llorente

Correspondence Authors:
José M Cuezva

All Authors:
Lucía González-Llorente,Fulvio Santacatterina,Ana García-Aguilar,Cristina Nuevo-Tapioles,Sara González-García,Zuzana Tirpakova,María Luisa Toribio,José M Cuezva