通过 IGF2 介导的自噬作用将成纤维细胞重编程为癌症相关成纤维细胞，促进肺癌细胞的转移

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2024-10-28 DOI:10.1016/j.isci.2024.111269

Limin Cao , Bingbing Li , Sijia Zheng , Qicheng Zhang , Yongmei Qian , Yinghui Ren , Huimin Wang , Min Wang , Xiang Wu , Jiayi Zhang , Ke Xu

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引用次数: 0

摘要

癌症相关成纤维细胞（CAFs）是基质细胞的主要组成部分。越来越多的证据表明，CAFs 可促进肿瘤生长和转移；然而，肿瘤细胞将正常成纤维细胞（NFs）重编程为 CAFs 的过程在很大程度上仍不为人知。在这项研究中，我们发现非小细胞肺癌（NSCLC）细胞通过自噬诱导将 NFs 活化为 CAFs。NSCLC细胞分泌的胰岛素样生长因子2（IGF2）介导了NSCLC细胞对自噬诱导和CAFs活化的影响。重要的是，活化的CAFs促进了NSCLC细胞的生长、迁移和侵袭。进一步的研究表明，活化的CAFs通过促进上皮-间质转化（EMT）过程、上调转移相关基因、释放CXCL12以及激活其下游的AKT丝氨酸/苏氨酸激酶1（AKT）/核因子κB（NF-κB）信号通路来促进NSCLC细胞的侵袭。这些发现揭示了IGF2介导的自噬在CAFs活化中起着关键作用，并表明成纤维细胞中的IGF2自噬级联可能是肺癌治疗的潜在靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Reprogramming of fibroblasts into cancer-associated fibroblasts via IGF2-mediated autophagy promotes metastasis of lung cancer cells

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Reprogramming of fibroblasts into cancer-associated fibroblasts via IGF2-mediated autophagy promotes metastasis of lung cancer cells

Cancer-associated fibroblasts (CAFs) are major component of stromal cells. Growing evidence suggests that CAFs promote tumor growth and metastasis; however, the reprogramming of normal fibroblasts (NFs) into CAFs by tumor cells still remains largely unknown. In this study, we found that non-small cell lung cancer (NSCLC) cells activated NFs into CAFs via autophagy induction. Insulin-like growth factor 2 (IGF2) secreted by NSCLC cells mediated NSCLC cells’ effect on autophagy induction and CAFs activation. Importantly, the activated CAFs promoted NSCLC cells growth, migration, and invasion. Further study showed that the activated CAFs facilitated NSCLC cells invasion via promoting epithelial-mesenchymal transition (EMT) process, upregulating metastasis-related genes, releasing CXCL12, and activating its downstream AKT serine/threonine kinase 1 (AKT)/ nuclear factor κB (NF-κB) signaling pathway. These findings revealed that IGF2-mediated autophagy plays a critical role in CAFs activation and suggested the IGF2-autophagy cascade in fibroblasts could be a potential target for lung cancer therapy.

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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