Cancer-associated fibroblasts facilitate DNA damage repair by promoting the glycolysis in non-small cell lung cancer
Radiotherapy is an essential treatment modality for the management of non-small cell lung cancer (NSCLC) patients. Tumor radioresistance is the major factor limiting the efficacy of radiotherapy in NSCLC patients. Our study aimed to reveal whether cancer-associated fibroblasts (CAFs), one main compo...
Gespeichert in:
Veröffentlicht in: | Biochimica et biophysica acta. Molecular basis of disease 2023-06, Vol.1869 (5), p.166670-166670, Article 166670 |
---|---|
Hauptverfasser: | , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 166670 |
---|---|
container_issue | 5 |
container_start_page | 166670 |
container_title | Biochimica et biophysica acta. Molecular basis of disease |
container_volume | 1869 |
creator | Zhang, Hongfang Zhang, Ke Qiu, Liqing Yue, Jing Jiang, Hong Deng, Qinghua Zhou, Rongjing Yin, Zihao Ma, Shenglin Ke, Yuehai |
description | Radiotherapy is an essential treatment modality for the management of non-small cell lung cancer (NSCLC) patients. Tumor radioresistance is the major factor limiting the efficacy of radiotherapy in NSCLC patients. Our study aimed to reveal whether cancer-associated fibroblasts (CAFs), one main component of the tumor microenvironment, regulated DNA damage response of NSCLC cells following irradiation and clarify the involved mechanisms. We found CAFs inhibited irradiation-induced DNA damage while promoted DNA repair of NSCLC cells and caused cell cycle arrest in the radioresistant S phase. CAFs have the ability of up-regulating and stabilizing c-Myc, leading to the transcription activation of HK2 kinase, a key rate-limiting enzyme in glycolysis by activating Wnt/β-catenin pathway. Attenuation of glycolysis significantly reversed the effect of CAFs on DNA damage response of NSCLC cells. By high-throughput screening of human cytokines/chemokines array, we found CAFs-secreted midkine led to the promotion of glycolysis by activating Wnt/β-catenin pathway in NSCLC cells. In vivo, CAFs caused the radioresistance of NSCLC cells also by promoting the glycolysis in a β-catenin signaling-dependent manner. These findings may provide novel strategies for reversing the radioresistance of NSCLC cells.
•CAFs regulate DNA damage response of NSCLC cells by promoting glycolysis.•Inhibition of glycolysis reversed CAFs-induced radioresistance of NSCLC cells.•CAFs promote the glycolysis of NSCLC cells by secreting midkine.•CAFs-secreted midkine initiates the activation of β-catenin/c-myc/HK2 signaling axis. |
doi_str_mv | 10.1016/j.bbadis.2023.166670 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2780080636</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0925443923000364</els_id><sourcerecordid>2780080636</sourcerecordid><originalsourceid>FETCH-LOGICAL-c362t-588f1e93e05de334d9ea2e725b2fc967f8c3af7f7428a7c6307412acc45498563</originalsourceid><addsrcrecordid>eNp9kMGOFCEQhonRuLOrb2AMRy890kADfTHZzOpqstGLJt4ITRcjk-5mpBiTeXsZe_UohyIhX9VffIS8atm2Za16e9gOgxsjbjnjYtsqpTR7Qjat0X3DFfv-lGxYz7tGStFfkWvEA6unQs_JlVCGcyn7DSk7t3jIjUNMProCIw1xyGmYHBakwfk4xVLf6d3nWzq62e2BZji6mOlwpsec5lTisqflB9D9dPZpOmNEGhe6pKXB2U0T9VDLdKqU_5P2gjwLbkJ4-XjfkG8f3n_dfWwevtx_2t0-NF4oXprOmNBCL4B1Iwghxx4cB827gQffKx2MFy7ooCU3TnslmJYtd97LTvamU-KGvFnn1jV_ngCLnSNelnELpBNarg1jhilxQeWK-pwQMwR7zHF2-WxbZi--7cGuvu3Ft11917bXjwmnYYbxX9NfwRV4twJQ__krQrboI1QJY8zgix1T_H_Cb0Epk_0</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2780080636</pqid></control><display><type>article</type><title>Cancer-associated fibroblasts facilitate DNA damage repair by promoting the glycolysis in non-small cell lung cancer</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Zhang, Hongfang ; Zhang, Ke ; Qiu, Liqing ; Yue, Jing ; Jiang, Hong ; Deng, Qinghua ; Zhou, Rongjing ; Yin, Zihao ; Ma, Shenglin ; Ke, Yuehai</creator><creatorcontrib>Zhang, Hongfang ; Zhang, Ke ; Qiu, Liqing ; Yue, Jing ; Jiang, Hong ; Deng, Qinghua ; Zhou, Rongjing ; Yin, Zihao ; Ma, Shenglin ; Ke, Yuehai</creatorcontrib><description>Radiotherapy is an essential treatment modality for the management of non-small cell lung cancer (NSCLC) patients. Tumor radioresistance is the major factor limiting the efficacy of radiotherapy in NSCLC patients. Our study aimed to reveal whether cancer-associated fibroblasts (CAFs), one main component of the tumor microenvironment, regulated DNA damage response of NSCLC cells following irradiation and clarify the involved mechanisms. We found CAFs inhibited irradiation-induced DNA damage while promoted DNA repair of NSCLC cells and caused cell cycle arrest in the radioresistant S phase. CAFs have the ability of up-regulating and stabilizing c-Myc, leading to the transcription activation of HK2 kinase, a key rate-limiting enzyme in glycolysis by activating Wnt/β-catenin pathway. Attenuation of glycolysis significantly reversed the effect of CAFs on DNA damage response of NSCLC cells. By high-throughput screening of human cytokines/chemokines array, we found CAFs-secreted midkine led to the promotion of glycolysis by activating Wnt/β-catenin pathway in NSCLC cells. In vivo, CAFs caused the radioresistance of NSCLC cells also by promoting the glycolysis in a β-catenin signaling-dependent manner. These findings may provide novel strategies for reversing the radioresistance of NSCLC cells.
•CAFs regulate DNA damage response of NSCLC cells by promoting glycolysis.•Inhibition of glycolysis reversed CAFs-induced radioresistance of NSCLC cells.•CAFs promote the glycolysis of NSCLC cells by secreting midkine.•CAFs-secreted midkine initiates the activation of β-catenin/c-myc/HK2 signaling axis.</description><identifier>ISSN: 0925-4439</identifier><identifier>EISSN: 1879-260X</identifier><identifier>DOI: 10.1016/j.bbadis.2023.166670</identifier><identifier>PMID: 36822449</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>beta Catenin - genetics ; beta Catenin - metabolism ; CAFs ; Cancer-Associated Fibroblasts - pathology ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - metabolism ; Carcinoma, Non-Small-Cell Lung - radiotherapy ; DNA Damage ; DNA damage response ; DNA Repair ; Glycolysis ; Humans ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Lung Neoplasms - radiotherapy ; Midkine ; NSCLC ; Tumor Microenvironment ; Wnt Signaling Pathway - genetics</subject><ispartof>Biochimica et biophysica acta. Molecular basis of disease, 2023-06, Vol.1869 (5), p.166670-166670, Article 166670</ispartof><rights>2023</rights><rights>Copyright © 2023. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-588f1e93e05de334d9ea2e725b2fc967f8c3af7f7428a7c6307412acc45498563</citedby><cites>FETCH-LOGICAL-c362t-588f1e93e05de334d9ea2e725b2fc967f8c3af7f7428a7c6307412acc45498563</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbadis.2023.166670$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36822449$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Hongfang</creatorcontrib><creatorcontrib>Zhang, Ke</creatorcontrib><creatorcontrib>Qiu, Liqing</creatorcontrib><creatorcontrib>Yue, Jing</creatorcontrib><creatorcontrib>Jiang, Hong</creatorcontrib><creatorcontrib>Deng, Qinghua</creatorcontrib><creatorcontrib>Zhou, Rongjing</creatorcontrib><creatorcontrib>Yin, Zihao</creatorcontrib><creatorcontrib>Ma, Shenglin</creatorcontrib><creatorcontrib>Ke, Yuehai</creatorcontrib><title>Cancer-associated fibroblasts facilitate DNA damage repair by promoting the glycolysis in non-small cell lung cancer</title><title>Biochimica et biophysica acta. Molecular basis of disease</title><addtitle>Biochim Biophys Acta Mol Basis Dis</addtitle><description>Radiotherapy is an essential treatment modality for the management of non-small cell lung cancer (NSCLC) patients. Tumor radioresistance is the major factor limiting the efficacy of radiotherapy in NSCLC patients. Our study aimed to reveal whether cancer-associated fibroblasts (CAFs), one main component of the tumor microenvironment, regulated DNA damage response of NSCLC cells following irradiation and clarify the involved mechanisms. We found CAFs inhibited irradiation-induced DNA damage while promoted DNA repair of NSCLC cells and caused cell cycle arrest in the radioresistant S phase. CAFs have the ability of up-regulating and stabilizing c-Myc, leading to the transcription activation of HK2 kinase, a key rate-limiting enzyme in glycolysis by activating Wnt/β-catenin pathway. Attenuation of glycolysis significantly reversed the effect of CAFs on DNA damage response of NSCLC cells. By high-throughput screening of human cytokines/chemokines array, we found CAFs-secreted midkine led to the promotion of glycolysis by activating Wnt/β-catenin pathway in NSCLC cells. In vivo, CAFs caused the radioresistance of NSCLC cells also by promoting the glycolysis in a β-catenin signaling-dependent manner. These findings may provide novel strategies for reversing the radioresistance of NSCLC cells.
•CAFs regulate DNA damage response of NSCLC cells by promoting glycolysis.•Inhibition of glycolysis reversed CAFs-induced radioresistance of NSCLC cells.•CAFs promote the glycolysis of NSCLC cells by secreting midkine.•CAFs-secreted midkine initiates the activation of β-catenin/c-myc/HK2 signaling axis.</description><subject>beta Catenin - genetics</subject><subject>beta Catenin - metabolism</subject><subject>CAFs</subject><subject>Cancer-Associated Fibroblasts - pathology</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Carcinoma, Non-Small-Cell Lung - radiotherapy</subject><subject>DNA Damage</subject><subject>DNA damage response</subject><subject>DNA Repair</subject><subject>Glycolysis</subject><subject>Humans</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - radiotherapy</subject><subject>Midkine</subject><subject>NSCLC</subject><subject>Tumor Microenvironment</subject><subject>Wnt Signaling Pathway - genetics</subject><issn>0925-4439</issn><issn>1879-260X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMGOFCEQhonRuLOrb2AMRy890kADfTHZzOpqstGLJt4ITRcjk-5mpBiTeXsZe_UohyIhX9VffIS8atm2Za16e9gOgxsjbjnjYtsqpTR7Qjat0X3DFfv-lGxYz7tGStFfkWvEA6unQs_JlVCGcyn7DSk7t3jIjUNMProCIw1xyGmYHBakwfk4xVLf6d3nWzq62e2BZji6mOlwpsec5lTisqflB9D9dPZpOmNEGhe6pKXB2U0T9VDLdKqU_5P2gjwLbkJ4-XjfkG8f3n_dfWwevtx_2t0-NF4oXprOmNBCL4B1Iwghxx4cB827gQffKx2MFy7ooCU3TnslmJYtd97LTvamU-KGvFnn1jV_ngCLnSNelnELpBNarg1jhilxQeWK-pwQMwR7zHF2-WxbZi--7cGuvu3Ft11917bXjwmnYYbxX9NfwRV4twJQ__krQrboI1QJY8zgix1T_H_Cb0Epk_0</recordid><startdate>202306</startdate><enddate>202306</enddate><creator>Zhang, Hongfang</creator><creator>Zhang, Ke</creator><creator>Qiu, Liqing</creator><creator>Yue, Jing</creator><creator>Jiang, Hong</creator><creator>Deng, Qinghua</creator><creator>Zhou, Rongjing</creator><creator>Yin, Zihao</creator><creator>Ma, Shenglin</creator><creator>Ke, Yuehai</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202306</creationdate><title>Cancer-associated fibroblasts facilitate DNA damage repair by promoting the glycolysis in non-small cell lung cancer</title><author>Zhang, Hongfang ; Zhang, Ke ; Qiu, Liqing ; Yue, Jing ; Jiang, Hong ; Deng, Qinghua ; Zhou, Rongjing ; Yin, Zihao ; Ma, Shenglin ; Ke, Yuehai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-588f1e93e05de334d9ea2e725b2fc967f8c3af7f7428a7c6307412acc45498563</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>beta Catenin - genetics</topic><topic>beta Catenin - metabolism</topic><topic>CAFs</topic><topic>Cancer-Associated Fibroblasts - pathology</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - metabolism</topic><topic>Carcinoma, Non-Small-Cell Lung - radiotherapy</topic><topic>DNA Damage</topic><topic>DNA damage response</topic><topic>DNA Repair</topic><topic>Glycolysis</topic><topic>Humans</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - radiotherapy</topic><topic>Midkine</topic><topic>NSCLC</topic><topic>Tumor Microenvironment</topic><topic>Wnt Signaling Pathway - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Hongfang</creatorcontrib><creatorcontrib>Zhang, Ke</creatorcontrib><creatorcontrib>Qiu, Liqing</creatorcontrib><creatorcontrib>Yue, Jing</creatorcontrib><creatorcontrib>Jiang, Hong</creatorcontrib><creatorcontrib>Deng, Qinghua</creatorcontrib><creatorcontrib>Zhou, Rongjing</creatorcontrib><creatorcontrib>Yin, Zihao</creatorcontrib><creatorcontrib>Ma, Shenglin</creatorcontrib><creatorcontrib>Ke, Yuehai</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biochimica et biophysica acta. Molecular basis of disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Hongfang</au><au>Zhang, Ke</au><au>Qiu, Liqing</au><au>Yue, Jing</au><au>Jiang, Hong</au><au>Deng, Qinghua</au><au>Zhou, Rongjing</au><au>Yin, Zihao</au><au>Ma, Shenglin</au><au>Ke, Yuehai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cancer-associated fibroblasts facilitate DNA damage repair by promoting the glycolysis in non-small cell lung cancer</atitle><jtitle>Biochimica et biophysica acta. Molecular basis of disease</jtitle><addtitle>Biochim Biophys Acta Mol Basis Dis</addtitle><date>2023-06</date><risdate>2023</risdate><volume>1869</volume><issue>5</issue><spage>166670</spage><epage>166670</epage><pages>166670-166670</pages><artnum>166670</artnum><issn>0925-4439</issn><eissn>1879-260X</eissn><abstract>Radiotherapy is an essential treatment modality for the management of non-small cell lung cancer (NSCLC) patients. Tumor radioresistance is the major factor limiting the efficacy of radiotherapy in NSCLC patients. Our study aimed to reveal whether cancer-associated fibroblasts (CAFs), one main component of the tumor microenvironment, regulated DNA damage response of NSCLC cells following irradiation and clarify the involved mechanisms. We found CAFs inhibited irradiation-induced DNA damage while promoted DNA repair of NSCLC cells and caused cell cycle arrest in the radioresistant S phase. CAFs have the ability of up-regulating and stabilizing c-Myc, leading to the transcription activation of HK2 kinase, a key rate-limiting enzyme in glycolysis by activating Wnt/β-catenin pathway. Attenuation of glycolysis significantly reversed the effect of CAFs on DNA damage response of NSCLC cells. By high-throughput screening of human cytokines/chemokines array, we found CAFs-secreted midkine led to the promotion of glycolysis by activating Wnt/β-catenin pathway in NSCLC cells. In vivo, CAFs caused the radioresistance of NSCLC cells also by promoting the glycolysis in a β-catenin signaling-dependent manner. These findings may provide novel strategies for reversing the radioresistance of NSCLC cells.
•CAFs regulate DNA damage response of NSCLC cells by promoting glycolysis.•Inhibition of glycolysis reversed CAFs-induced radioresistance of NSCLC cells.•CAFs promote the glycolysis of NSCLC cells by secreting midkine.•CAFs-secreted midkine initiates the activation of β-catenin/c-myc/HK2 signaling axis.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>36822449</pmid><doi>10.1016/j.bbadis.2023.166670</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0925-4439 |
ispartof | Biochimica et biophysica acta. Molecular basis of disease, 2023-06, Vol.1869 (5), p.166670-166670, Article 166670 |
issn | 0925-4439 1879-260X |
language | eng |
recordid | cdi_proquest_miscellaneous_2780080636 |
source | MEDLINE; Elsevier ScienceDirect Journals Complete; EZB-FREE-00999 freely available EZB journals |
subjects | beta Catenin - genetics beta Catenin - metabolism CAFs Cancer-Associated Fibroblasts - pathology Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - metabolism Carcinoma, Non-Small-Cell Lung - radiotherapy DNA Damage DNA damage response DNA Repair Glycolysis Humans Lung Neoplasms - genetics Lung Neoplasms - metabolism Lung Neoplasms - radiotherapy Midkine NSCLC Tumor Microenvironment Wnt Signaling Pathway - genetics |
title | Cancer-associated fibroblasts facilitate DNA damage repair by promoting the glycolysis in non-small cell lung cancer |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T11%3A52%3A46IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cancer-associated%20fibroblasts%20facilitate%20DNA%20damage%20repair%20by%20promoting%20the%20glycolysis%20in%20non-small%20cell%20lung%20cancer&rft.jtitle=Biochimica%20et%20biophysica%20acta.%20Molecular%20basis%20of%20disease&rft.au=Zhang,%20Hongfang&rft.date=2023-06&rft.volume=1869&rft.issue=5&rft.spage=166670&rft.epage=166670&rft.pages=166670-166670&rft.artnum=166670&rft.issn=0925-4439&rft.eissn=1879-260X&rft_id=info:doi/10.1016/j.bbadis.2023.166670&rft_dat=%3Cproquest_cross%3E2780080636%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2780080636&rft_id=info:pmid/36822449&rft_els_id=S0925443923000364&rfr_iscdi=true |