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PDPN(+) CAFs facilitate the motility of OSCC cells by inhibiting ferroptosis via transferring exosomal lncRNA FTX

Cancer-associated fibroblasts (CAFs) are abundant and heterogeneous in tumor microenvironment (TME). Cross-talk between cancer cells and CAFs results in cancer progression. Here, we demonstrated that a distinct cancer-associated fibroblasts subset with podoplanin (PDPN) positive expression (PDPN(+)...

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Autores principales: Li, Yaoyin, Ma, Zeyi, Li, Weiyu, Xu, Xiaoqing, Shen, Peiqi, Zhang, Si-en, Cheng, Bin, Xia, Juan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10665425/
https://www.ncbi.nlm.nih.gov/pubmed/37993428
http://dx.doi.org/10.1038/s41419-023-06280-3
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author Li, Yaoyin
Ma, Zeyi
Li, Weiyu
Xu, Xiaoqing
Shen, Peiqi
Zhang, Si-en
Cheng, Bin
Xia, Juan
author_facet Li, Yaoyin
Ma, Zeyi
Li, Weiyu
Xu, Xiaoqing
Shen, Peiqi
Zhang, Si-en
Cheng, Bin
Xia, Juan
author_sort Li, Yaoyin
collection PubMed
description Cancer-associated fibroblasts (CAFs) are abundant and heterogeneous in tumor microenvironment (TME). Cross-talk between cancer cells and CAFs results in cancer progression. Here, we demonstrated that a distinct cancer-associated fibroblasts subset with podoplanin (PDPN) positive expression (PDPN(+) CAFs) was correlated with poor survival in oral squamous cell carcinoma (OSCC). PDPN(+) CAFs promoted the progression of OSCC by transferring exosomal lncRNA FTX to OSCC cells. Mechanically, FTX bound to flap endonuclease-1 (FEN1), forming an RNA‒protein complex. FTX enhanced promoter demethylation of FEN1 by recruiting ten-eleven translocation-2 (TET2). In addition, FTX/FEN1 axis promoted OSCC cells motility by inhibiting ferroptosis. In xenograft experiments, RSL-3, a ferroptosis-inducing agent, suppressed the tumorigenesis potential of FEN1-overexpressed OSCC cells. Furthermore, Acyl-CoA synthetase long-chain family member 4 (ACSL4) was confirmed to participate in the motility promotion induced by FEN1 overexpression. FEN1 could bind to promoter region of ACSL4 and then inhibit ferroptosis in OSCC cells. Our study reveals that PDPN(+) CAFs promote the invasiveness of OSCC cells by inhibiting ferroptosis through FTX/FEN1/ACSL4 signaling cascade. PDPN(+) CAFs may serve as a novel potential therapeutic target for OSCC.
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spelling pubmed-106654252023-11-22 PDPN(+) CAFs facilitate the motility of OSCC cells by inhibiting ferroptosis via transferring exosomal lncRNA FTX Li, Yaoyin Ma, Zeyi Li, Weiyu Xu, Xiaoqing Shen, Peiqi Zhang, Si-en Cheng, Bin Xia, Juan Cell Death Dis Article Cancer-associated fibroblasts (CAFs) are abundant and heterogeneous in tumor microenvironment (TME). Cross-talk between cancer cells and CAFs results in cancer progression. Here, we demonstrated that a distinct cancer-associated fibroblasts subset with podoplanin (PDPN) positive expression (PDPN(+) CAFs) was correlated with poor survival in oral squamous cell carcinoma (OSCC). PDPN(+) CAFs promoted the progression of OSCC by transferring exosomal lncRNA FTX to OSCC cells. Mechanically, FTX bound to flap endonuclease-1 (FEN1), forming an RNA‒protein complex. FTX enhanced promoter demethylation of FEN1 by recruiting ten-eleven translocation-2 (TET2). In addition, FTX/FEN1 axis promoted OSCC cells motility by inhibiting ferroptosis. In xenograft experiments, RSL-3, a ferroptosis-inducing agent, suppressed the tumorigenesis potential of FEN1-overexpressed OSCC cells. Furthermore, Acyl-CoA synthetase long-chain family member 4 (ACSL4) was confirmed to participate in the motility promotion induced by FEN1 overexpression. FEN1 could bind to promoter region of ACSL4 and then inhibit ferroptosis in OSCC cells. Our study reveals that PDPN(+) CAFs promote the invasiveness of OSCC cells by inhibiting ferroptosis through FTX/FEN1/ACSL4 signaling cascade. PDPN(+) CAFs may serve as a novel potential therapeutic target for OSCC. Nature Publishing Group UK 2023-11-22 /pmc/articles/PMC10665425/ /pubmed/37993428 http://dx.doi.org/10.1038/s41419-023-06280-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Li, Yaoyin
Ma, Zeyi
Li, Weiyu
Xu, Xiaoqing
Shen, Peiqi
Zhang, Si-en
Cheng, Bin
Xia, Juan
PDPN(+) CAFs facilitate the motility of OSCC cells by inhibiting ferroptosis via transferring exosomal lncRNA FTX
title PDPN(+) CAFs facilitate the motility of OSCC cells by inhibiting ferroptosis via transferring exosomal lncRNA FTX
title_full PDPN(+) CAFs facilitate the motility of OSCC cells by inhibiting ferroptosis via transferring exosomal lncRNA FTX
title_fullStr PDPN(+) CAFs facilitate the motility of OSCC cells by inhibiting ferroptosis via transferring exosomal lncRNA FTX
title_full_unstemmed PDPN(+) CAFs facilitate the motility of OSCC cells by inhibiting ferroptosis via transferring exosomal lncRNA FTX
title_short PDPN(+) CAFs facilitate the motility of OSCC cells by inhibiting ferroptosis via transferring exosomal lncRNA FTX
title_sort pdpn(+) cafs facilitate the motility of oscc cells by inhibiting ferroptosis via transferring exosomal lncrna ftx
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10665425/
https://www.ncbi.nlm.nih.gov/pubmed/37993428
http://dx.doi.org/10.1038/s41419-023-06280-3
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