دورية أكاديمية
The glutathione S-transferase Gstt1 drives survival and dissemination in metastases.
| العنوان: | The glutathione S-transferase Gstt1 drives survival and dissemination in metastases. |
|---|---|
| المؤلفون: | Ferrer CM; The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA. cferrer@som.umaryland.edu.; The Broad Institute of Harvard and MIT, Cambridge, MA, USA. cferrer@som.umaryland.edu.; University of Maryland School of Medicine and the Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA. cferrer@som.umaryland.edu., Cho HM; The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.; The Broad Institute of Harvard and MIT, Cambridge, MA, USA., Boon R; The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.; Galapagos NV, 2800 Mechelen, Belgium., Bernasocchi T; The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.; The Broad Institute of Harvard and MIT, Cambridge, MA, USA., Wong LP; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA., Cetinbas M; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA., Haggerty ER; The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA., Mitsiades I; The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA., Wojtkiewicz GR; Center for Systems Biology, Massachusetts General Hospital, Boston, MA, USA., McLoughlin DE; The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.; Termeer Center for Targeted Therapies, Massachusetts General Hospital, Boston, MA, USA., Aboushousha R; University of Vermont Larner College of Medicine, Burlington, VT, USA., Abdelhamid H; University of Vermont Larner College of Medicine, Burlington, VT, USA., Kugel S; Fred Hutchison Cancer Research Center, Seattle, WA, USA., Rheinbay E; The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA., Sadreyev R; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA., Juric D; The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.; Termeer Center for Targeted Therapies, Massachusetts General Hospital, Boston, MA, USA., Janssen-Heininger YMW; University of Vermont Larner College of Medicine, Burlington, VT, USA., Mostoslavsky R; The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA. rmostoslavsky@mgh.harvard.edu.; The Broad Institute of Harvard and MIT, Cambridge, MA, USA. rmostoslavsky@mgh.harvard.edu. |
| المصدر: | Nature cell biology [Nat Cell Biol] 2024 Jun; Vol. 26 (6), pp. 975-990. Date of Electronic Publication: 2024 Jun 11. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Macmillan Magazines Ltd Country of Publication: England NLM ID: 100890575 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4679 (Electronic) Linking ISSN: 14657392 NLM ISO Abbreviation: Nat Cell Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : Macmillan Magazines Ltd., [1999- |
| مواضيع طبية MeSH: | Glutathione Transferase*/metabolism , Glutathione Transferase*/genetics , Pancreatic Neoplasms*/pathology , Pancreatic Neoplasms*/genetics , Pancreatic Neoplasms*/enzymology , Pancreatic Neoplasms*/metabolism , Tumor Microenvironment*, Humans ; Animals ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; Fibronectins/metabolism ; Neoplasm Metastasis ; Adenocarcinoma/genetics ; Adenocarcinoma/pathology ; Adenocarcinoma/metabolism ; Adenocarcinoma/enzymology ; Cell Survival ; Gene Expression Regulation, Neoplastic ; Mice ; Female ; Mice, Inbred C57BL |
| مستخلص: | Identifying the adaptive mechanisms of metastatic cancer cells remains an elusive question in the treatment of metastatic disease, particularly in pancreatic cancer (pancreatic adenocarcinoma, PDA). A loss-of-function shRNA targeted screen in metastatic-derived cells identified Gstt1, a member of the glutathione S-transferase superfamily, as uniquely required for dissemination and metastasis, but dispensable for primary tumour growth. Gstt1 is expressed in latent disseminated tumour cells (DTCs), is retained within a subpopulation of slow-cycling cells within existing metastases, and its inhibition leads to complete regression of macrometastatic tumours. This distinct Gstt1 high population is highly metastatic and retains slow-cycling phenotypes, epithelial-mesenchymal transition features and DTC characteristics compared to the Gstt1 low population. Mechanistic studies indicate that in this subset of cancer cells, Gstt1 maintains metastases by binding and glutathione-modifying intracellular fibronectin, in turn promoting its secretion and deposition into the metastatic microenvironment. We identified Gstt1 as a mediator of metastasis, highlighting the importance of heterogeneity and its influence on the metastatic tumour microenvironment. (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.) |
| References: | Weiss, L. Metastatic inefficiency. Adv. Cancer Res. 54, 159–211 (1990). (PMID: 168868110.1016/S0065-230X(08)60811-8) Anderson, R. L. et al. A framework for the development of effective anti-metastatic agents. Nat. Rev. Clin. Oncol. 16, 185–204 (2019). (PMID: 3051497710.1038/s41571-018-0134-8) Lambert, A. W., Pattabiraman, D. R. & Weinberg, R. A. Emerging biological principles of metastasis. Cell 168, 670–691 (2017). (PMID: 28187288530846510.1016/j.cell.2016.11.037) Maddipati, R. & Stanger, B. Z. Pancreatic cancer metastases harbor evidence of polyclonality. Cancer Discov. 5, 1086–1097 (2015). (PMID: 26209539465773010.1158/2159-8290.CD-15-0120) Makohon-Moore, A. P. et al. Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer. Nat. Genet. 49, 358–366 (2017). (PMID: 28092682566343910.1038/ng.3764) McDonald, O. G. et al. Epigenomic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis. Nat. Genet. 49, 367–376 (2017). (PMID: 28092686569568210.1038/ng.3753) Roe, J. S. et al. Enhancer reprogramming promotes pancreatic cancer metastasis. Cell 170, 875–888 (2017). (PMID: 28757253572627710.1016/j.cell.2017.07.007) Pommier, A. et al. Unresolved endoplasmic reticulum stress engenders immune-resistant, latent pancreatic cancer metastases. Science 360, eaao4908 (2018). (PMID: 29773669654738010.1126/science.aao4908) Mostoslavsky, R. & Bardeesy, N. Reprogramming enhancers to drive metastasis. Cell 170, 823–825 (2017). (PMID: 2884141410.1016/j.cell.2017.08.010) Chiou, S. H. et al. BLIMP1 induces transient metastatic heterogeneity in pancreatic cancer. Cancer Discov. 7, 1184–1199 (2017). (PMID: 28790031562814510.1158/2159-8290.CD-17-0250) Maddipati, R. et al. Myc levels regulate metastatic heterogeneity in pancreatic adenocarcinoma. Cancer Discov. 12, 542–561 (2022). (PMID: 3455196810.1158/2159-8290.CD-20-1826) Hosseini, H. et al. Early dissemination seeds metastasis in breast cancer. Nature 540, 552–558 (2016). (PMID: 27974799539086410.1038/nature20785) Klein, C. A. Parallel progression of primary tumours and metastases. Nat. Rev. Cancer 9, 302–312 (2009). (PMID: 1930806910.1038/nrc2627) Hüsemann, Y. et al. Systemic spread is an early step in breast cancer. Cancer Cell 13, 58–68 (2008). (PMID: 1816734010.1016/j.ccr.2007.12.003) Rhim, A. D. et al. EMT and dissemination precede pancreatic tumor formation. Cell 148, 349–361 (2012). (PMID: 22265420326654210.1016/j.cell.2011.11.025) Ryan, D. P., Hong, T. S. & Bardeesy, N. Pancreatic adenocarcinoma. N. Engl. J. Med. 371, 2140–2141 (2014). (PMID: 2542712310.1056/NEJMra1404198) Giancotti, F. G. Mechanisms governing metastatic dormancy and reactivation. Cell 155, 750–764 (2013). (PMID: 24209616435473410.1016/j.cell.2013.10.029) Ting, D. T. et al. Single-cell RNA sequencing identifies extracellular matrix gene expression by pancreatic circulating tumor cells. Cell Rep. 8, 1905–1918 (2014). (PMID: 25242334423032510.1016/j.celrep.2014.08.029) Gao, H. et al. Forward genetic screens in mice uncover mediators and suppressors of metastatic reactivation. Proc. Natl Acad. Sci. USA 111, 16532–16537 (2014). (PMID: 25378704424634910.1073/pnas.1403234111) Kugel, S. et al. SIRT6 suppresses pancreatic cancer through control of Lin28b. Cell 165, 1401–1415 (2016). (PMID: 27180906489298310.1016/j.cell.2016.04.033) Siegel, R. L., Miller, K. D., Fuchs, H. E. & Jemal, A. Cancer statistics, 2022. CA Cancer J. Clin. 72, 7–33 (2022). (PMID: 3502020410.3322/caac.21708) Aslakson, C. J. & Miller, F. R. Selective events in the metastatic process defined by analysis of the sequential dissemination of subpopulations of a mouse mammary tumor. Cancer Res. 52, 1399–1405 (1992). (PMID: 1540948) Gobeil, S., Zhu, X., Doillon, C. J. & Green, M. R. A genome-wide shRNA screen identifies GAS1 as a novel melanoma metastasis suppressor gene. Genes Dev. 22, 2932–2940 (2008). (PMID: 18981472257779010.1101/gad.1714608) van der Weyden, L. et al. Genome-wide in vivo screen identifies novel host regulators of metastatic colonization. Nature 541, 233–236 (2017). (PMID: 28052056560328610.1038/nature20792) Xia, F. et al. Genome-wide in vivo screen of circulating tumor cells identifies. Sci. Adv. 8, eabo7792 (2022). (PMID: 360543481084895310.1126/sciadv.abo7792) Celià-Terrassa, T. & Kang, Y. Distinctive properties of metastasis-initiating cells. Genes Dev. 30, 892–908 (2016). (PMID: 27083997484029610.1101/gad.277681.116) Townsend, D. M. & Tew, K. D. The role of glutathione-S-transferase in anti-cancer drug resistance. Oncogene 22, 7369–7375 (2003). (PMID: 14576844636112510.1038/sj.onc.1206940) Townsend, D. & Tew, K. Cancer drugs, genetic variation and the glutathione-S-transferase gene family. Am. J. Pharmacogenomics 3, 157–172 (2003). (PMID: 12814324908671610.2165/00129785-200303030-00002) Allocati, N., Masulli, M., Di Ilio, C. & Federici, L. Glutathione transferases: substrates, inihibitors and pro-drugs in cancer and neurodegenerative diseases. Oncogenesis 7, 8 (2018). (PMID: 29362397583387310.1038/s41389-017-0025-3) Tars, K. et al. Structural basis of the suppressed catalytic activity of wild-type human glutathione transferase T1-1 compared to its W234R mutant. J. Mol. Biol. 355, 96–105 (2006). (PMID: 1629838810.1016/j.jmb.2005.10.049) Pascual, G. et al. Targeting metastasis-initiating cells through the fatty acid receptor CD36. Nature 541, 41–45 (2017). (PMID: 2797479310.1038/nature20791) Ganesh, K. et al. L1CAM defines the regenerative origin of metastasis-initiating cells in colorectal cancer. Nat. Cancer 1, 28–45 (2020). (PMID: 32656539735113410.1038/s43018-019-0006-x) Perego, M. et al. A slow-cycling subpopulation of melanoma cells with highly invasive properties. Oncogene 37, 302–312 (2018). (PMID: 2892540310.1038/onc.2017.341) Tew, K. D. & Townsend, D. M. Glutathione-S-transferases as determinants of cell survival and death. Antioxid. Redox Signal. 17, 1728–1737 (2012). (PMID: 22540427347419010.1089/ars.2012.4640) Amrutkar, M., Aasrum, M., Verbeke, C. S. & Gladhaug, I. P. Secretion of fibronectin by human pancreatic stellate cells promotes chemoresistance to gemcitabine in pancreatic cancer cells. BMC Cancer 19, 596 (2019). (PMID: 31208372658045310.1186/s12885-019-5803-1) Erdogan, B. et al. Cancer-associated fibroblasts promote directional cancer cell migration by aligning fibronectin. J. Cell Biol. 216, 3799–3816 (2017). (PMID: 29021221567489510.1083/jcb.201704053) Efthymiou, G. et al. Shaping up the tumor microenvironment with cellular fibronectin. Front. Oncol. 10, 641 (2020). (PMID: 32426283720347510.3389/fonc.2020.00641) Kaplan, R. N. et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438, 820–827 (2005). (PMID: 16341007294588210.1038/nature04186) Barney, L. E. et al. Tumor cell-organized fibronectin maintenance of a dormant breast cancer population. Sci. Adv. 6, eaaz4157 (2020). (PMID: 32195352706590410.1126/sciadv.aaz4157) Hu, D. et al. Stromal fibronectin expression in patients with resected pancreatic ductal adenocarcinoma. World J. Surg. Oncol. 17, 29 (2019). (PMID: 30736807636870210.1186/s12957-019-1574-z) Sahai, E. et al. A framework for advancing our understanding of cancer-associated fibroblasts. Nat. Rev. Cancer 20, 174–186 (2020). (PMID: 31980749704652910.1038/s41568-019-0238-1) Fane, M. E. et al. Stromal changes in the aged lung induce an emergence from melanoma dormancy. Nature 606, 396–405 (2022). (PMID: 35650435955495110.1038/s41586-022-04774-2) Le Gal, K. et al. Antioxidants can increase melanoma metastasis in mice. Sci. Transl. Med. 7, 308re308 (2015). Piskounova, E. et al. Oxidative stress inhibits distant metastasis by human melanoma cells. Nature 527, 186–191 (2015). (PMID: 26466563464410310.1038/nature15726) Arfsten, D. P., Johnson, E. W., Wilfong, E. R., Jung, A. E. & Bobb, A. J. Distribution of radio-labeled N-acetyl-L-cysteine in Sprague-Dawley rats and its effect on glutathione metabolism following single and repeat dosing by oral gavage. Cutan Ocul Toxicol 26, 113–134 (2007). (PMID: 1761297910.1080/15569520701212233) Ubellacker, J. M. et al. Lymph protects metastasizing melanoma cells from ferroptosis. Nature 585, 113–118 (2020). (PMID: 32814895748446810.1038/s41586-020-2623-z) Naba, A., Clauser, K. R., Lamar, J. M., Carr, S. A. & Hynes, R. O. Extracellular matrix signatures of human mammary carcinoma identify novel metastasis promoters. eLife 3, e01308 (2014). (PMID: 24618895394443710.7554/eLife.01308) Simpson, C. D., Anyiwe, K. & Schimmer, A. D. Anoikis resistance and tumor metastasis. Cancer Lett. 272, 177–185 (2008). (PMID: 1857928510.1016/j.canlet.2008.05.029) Labuschagne, C. F., Cheung, E. C., Blagih, J., Domart, M. C. & Vousden, K. H. Cell clustering promotes a metabolic switch that supports metastatic colonization. Cell Metab. 30, 720–734 (2019). (PMID: 31447323686339210.1016/j.cmet.2019.07.014) Hayes, J. D., Flanagan, J. U. & Jowsey, I. R. Glutathione transferases. Annu. Rev. Pharmacol. Toxicol. 45, 51–88 (2005). (PMID: 1582217110.1146/annurev.pharmtox.45.120403.095857) Simeonov, K. P. et al. Single-cell lineage tracing of metastatic cancer reveals selection of hybrid EMT states. Cancer Cell 39, 1150–1162 (2021). (PMID: 34115987878220710.1016/j.ccell.2021.05.005) Anders, S., Pyl, P. T. & Huber, W. HTSeq—a Python framework to work with high-throughput sequencing data. Bioinformatics 31, 166–169 (2015). (PMID: 2526070010.1093/bioinformatics/btu638) Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013). (PMID: 2310488610.1093/bioinformatics/bts635) Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139–140 (2010). (PMID: 1991030810.1093/bioinformatics/btp616) Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005). (PMID: 16199517123989610.1073/pnas.0506580102) Sherman, B. T. et al. DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res. 50, W216–W221 (2022). (PMID: 35325185925280510.1093/nar/gkac194) Huang, da W., Sherman, B. T. & Lempicki, R. A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4, 44–57 (2009). Lánczky, A. & Győrffy, B. Web-based survival analysis tool tailored for medical research (KMplot): development and implementation. J. Med. Internet Res. 23, e27633 (2021). (PMID: 34309564836712610.2196/27633) Shokeer, A., Larsson, A. K. & Mannervik, B. Residue 234 in glutathione transferase T1-1 plays a pivotal role in the catalytic activity and the selectivity against alternative substrates. Biochem. J. 388, 387–392 (2005). (PMID: 15683365118672910.1042/BJ20042064) Shokeer, A. & Mannervik, B. Residue 234 is a master switch of the alternative-substrate activity profile of human and rodent theta class glutathione transferase T1-1. Biochim. Biophys. Acta 1800, 466–473 (2010). (PMID: 2009726910.1016/j.bbagen.2010.01.003) Lawson, M. A. et al. Osteoclasts control reactivation of dormant myeloma cells by remodelling the endosteal niche. Nat. Commun. 6, 8983 (2015). (PMID: 2663227410.1038/ncomms9983) Bauer, J. A., Zámocká, M., Majtán, J. & Bauerová-Hlinková, V. Glucose oxidase, an enzyme ‘Ferrari’: its structure, function, production and properties in the light of various industrial and biotechnological applications. Biomolecules 12, 472 (2022). (PMID: 35327664894680910.3390/biom12030472) Danna, E. A. et al. Surgical removal of primary tumor reverses tumor-induced immunosuppression despite the presence of metastatic disease. Cancer Res. 64, 2205–2211 (2004). (PMID: 1502636410.1158/0008-5472.CAN-03-2646) Choi, J. E. et al. A unique subset of glycolytic tumour-propagating cells drives squamous cell carcinoma. Nat. Metab. 3, 182–195 (2021). (PMID: 33619381795408010.1038/s42255-021-00350-6) |
| معلومات مُعتمدة: | K99 CA252600 United States CA NCI NIH HHS; R00 CA252600 United States CA NCI NIH HHS; R01CA235412 U.S. Department of Health & Human Services | National Institutes of Health (NIH); R01GM128448 U.S. Department of Health & Human Services | National Institutes of Health (NIH) |
| المشرفين على المادة: | EC 2.5.1.18 (Glutathione Transferase) EC 2.5.1.- (glutathione S-transferase T1) 0 (Fibronectins) |
| تواريخ الأحداث: | Date Created: 20240611 Date Completed: 20240615 Latest Revision: 20240715 |
| رمز التحديث: | 20240715 |
| DOI: | 10.1038/s41556-024-01426-7 |
| PMID: | 38862786 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1476-4679 |
|---|---|
| DOI: | 10.1038/s41556-024-01426-7 |