Methionine secreted by tumor-associated pericytes supports cancer stem cells in clear cell renal carcinoma
Copyright © 2024 Elsevier Inc. All rights reserved..
Here, we identify a subset of vascular pericytes, defined by expression of platelet-derived growth factor receptor beta (PDGFR-β) and G-protein-coupled receptor 91 (GPR91), that promote tumorigenesis and tyrosine kinase inhibitors (TKIs) resistance by functioning as the primary methionine source for cancer stem cells (CSCs) in clear cell renal cell carcinoma (ccRCC). Tumor-cell-derived succinate binds to GPR91 on pericyte to activate autophagy for methionine production. CSCs use methionine to create stabilizing N6-methyladenosine in ATPase-family-AAA-domain-containing 2 (ATAD2) mRNA, and the resulting ATAD2 protein complexes with SRY-box transcription factor 9 to assemble super enhancers and thereby dictate its target genes that feature prominently in CSCs. Targeting PDGFR-β+GPR91+ pericytes with specific GRP91 antagonists reduce intratumoral methionine level, eliminate CSCs, and enhance TKIs sensitivity. These results unraveled the mechanisms by which PDGFR-β+GPR91+ pericytes provide supportive niche for CSCs and could be used to develop targets for treating ccRCC.
| Errataetall: |
CommentIn: Nat Rev Nephrol. 2024 Apr;20(4):203. - PMID 38409367 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:36 |
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| Enthalten in: |
Cell metabolism - 36(2024), 4 vom: 02. Apr., Seite 778-792.e10 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, ChuanJie [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 05.04.2024 Date Revised 05.04.2024 published: Print-Electronic CommentIn: Nat Rev Nephrol. 2024 Apr;20(4):203. - PMID 38409367 Citation Status MEDLINE |
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| doi: |
10.1016/j.cmet.2024.01.018 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Here, we identify a subset of vascular pericytes, defined by expression of platelet-derived growth factor receptor beta (PDGFR-β) and G-protein-coupled receptor 91 (GPR91), that promote tumorigenesis and tyrosine kinase inhibitors (TKIs) resistance by functioning as the primary methionine source for cancer stem cells (CSCs) in clear cell renal cell carcinoma (ccRCC). Tumor-cell-derived succinate binds to GPR91 on pericyte to activate autophagy for methionine production. CSCs use methionine to create stabilizing N6-methyladenosine in ATPase-family-AAA-domain-containing 2 (ATAD2) mRNA, and the resulting ATAD2 protein complexes with SRY-box transcription factor 9 to assemble super enhancers and thereby dictate its target genes that feature prominently in CSCs. Targeting PDGFR-β+GPR91+ pericytes with specific GRP91 antagonists reduce intratumoral methionine level, eliminate CSCs, and enhance TKIs sensitivity. These results unraveled the mechanisms by which PDGFR-β+GPR91+ pericytes provide supportive niche for CSCs and could be used to develop targets for treating ccRCC | ||
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| 700 | 1 | |a Gao, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Lim, Kiat Shenq |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, WenJie |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Hai |e verfasserin |4 aut | |
| 700 | 1 | |a He, HongChao |e verfasserin |4 aut | |
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| 700 | 1 | |a Xu, DanFeng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, QingQuan |e verfasserin |4 aut | |
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