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Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Nat. Rev. Mol. Cell Biol.<\/i>, 22<\/b>, 75\u201395 (2021).","DOI":"10.1038\/s41580-020-00314-w"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2) Sharpless NE, Sherr CJ. Forging a signature of in vivo<\/i> senescence. Nat. Rev. Cancer<\/i>, 15<\/b>, 397\u2013408 (2015).","DOI":"10.1038\/nrc3960"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3) Grosse L, Wagner N, Emelyanov A, Molina C, Lacas-Gervais S, Wagner K-D, Bulavin DV. Defined p16high<\/sup> senescent cell types are indispensable for mouse healthspan. Cell Metab.<\/i>, 32<\/b>, 87\u201399.e6 (2020).","DOI":"10.1016\/j.cmet.2020.05.002"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4) Omori S, Wang T-W, Johmura Y, et al<\/i>. Generation of a p16 reporter mouse and its use to characterize and target p16high<\/sup> cells in vivo<\/i>. Cell Metab.<\/i>, 32<\/b>, 814\u2013828.e6 (2020).","DOI":"10.1016\/j.cmet.2020.09.006"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5) Zhao H, Liu Z, Chen H, Han M, Zhang M, Liu K, Jin H, Liu X, Shi M, Pu W, Werner M, Meister M, Kauschke SG, Sun R, Wang J, Shen R, Wang Q-D, Ma X, Tchorz JS, Zhou B. Identifying specific functional roles for senescence across cell types. Cell<\/i>, 187<\/b>, 7314\u20137334.e21 (2024).","DOI":"10.1016\/j.cell.2024.09.021"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6) Faget DV, Ren Q, Stewart SA. Unmasking senescence: context-dependent effects of SASP in cancer. Nat. Rev. Cancer<\/i>, 19<\/b>, 439\u2013453 (2019).","DOI":"10.1038\/s41568-019-0156-2"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7) Sahai E, Astsaturov I, Cukierman E, et al<\/i>. A framework for advancing our understanding of cancer-associated fibroblasts. Nat. Rev. Cancer<\/i>, 20<\/b>, 174\u2013186 (2020).","DOI":"10.1038\/s41568-019-0238-1"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8) Assouline B, Kahn R, Hodali L, et al<\/i>. Senescent cancer-associated fibroblasts in pancreatic adenocarcinoma restrict CD8+<\/sup> T cell activation and limit responsiveness to immunotherapy in mice. Nat. Commun.<\/i>, 15<\/b>, 6162 (2024).","DOI":"10.1038\/s41467-024-50441-7"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9) Belle JI, Sen D, Baer JM, Liu X, Lander VE, Ye J, Sells BE, Knolhoff BL, Faiz A, Kang L-I, Qian G, Fields RC, Ding L, Kim H, Provenzano PP, Stewart SA, DeNardo DG. Senescence defines a distinct subset of myofibroblasts that orchestrates immunosuppression in pancreatic cancer. Cancer Discov.<\/i>, 14<\/b>, 1324\u20131355 (2024).","DOI":"10.1158\/2159-8290.CD-23-0428"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10) Ye J, Baer JM, Faget DV, Morikis VA, Ren Q, Melam A, Delgado AP, Luo X, Bagchi SM, Belle JI, Campos E, Friedman M, Veis DJ, Knudsen ES, Witkiewicz AK, Powers S, Longmore GD, DeNardo DG, Stewart SA. Senescent CAFs mediate immunosuppression and drive breast cancer progression. Cancer Discov.<\/i>, 14<\/b>, 1302\u20131323 (2024).","DOI":"10.1158\/2159-8290.CD-23-0426"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) Long GV, Swetter SM, Menzies AM, Gershenwald JE, Scolyer RA. Cutaneous melanoma. Lancet<\/i>, 402<\/b>, 485\u2013502 (2023).","DOI":"10.1016\/S0140-6736(23)00821-8"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Neesse A, Alg\u00fcl H, Tuveson DA, Gress TM. Stromal biology and therapy in pancreatic cancer: a changing paradigm. Gut<\/i>, 64<\/b>, 1476\u20131484 (2015).","DOI":"10.1136\/gutjnl-2015-309304"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) Gajewski TF, Schreiber H, Fu Y-X. Innate and adaptive immune cells in the tumor microenvironment. Nat. Immunol.<\/i>, 14<\/b>, 1014\u20131022 (2013).","DOI":"10.1038\/ni.2703"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14) Rambow F, Marine J-C, Goding CR. Melanoma plasticity and phenotypic diversity: therapeutic barriers and opportunities. Genes Dev.<\/i>, 33<\/b>, 1295\u20131318 (2019).","DOI":"10.1101\/gad.329771.119"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Wang J, Perry CJ, Meeth K, Thakral D, Damsky W, Micevic G, Kaech S, Blenman K, Bosenberg M. UV-induced somatic mutations elicit a functional T cell response in the YUMMER1.7 mouse melanoma model. Pigment Cell Melanoma Res.<\/i>, 30<\/b>, 428\u2013435 (2017).","DOI":"10.1111\/pcmr.12591"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16) Tomayko MM, Reynolds CP. Determination of subcutaneous tumor size in athymic (nude) mice. Cancer Chemother. Pharmacol.<\/i>, 24<\/b>, 148\u2013154 (1989).","DOI":"10.1007\/BF00300234"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17) Fleming SJ, Chaffin MD, Arduini A, Akkad A-D, Banks E, Marioni JC, Philippakis AA, Ellinor PT, Babadi M. Unsupervised removal of systematic background noise from droplet-based single-cell experiments using CellBender. Nat. Methods<\/i>, 20<\/b>, 1323\u20131335 (2023).","DOI":"10.1038\/s41592-023-01943-7"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18) Korsunsky I, Millard N, Fan J, Slowikowski K, Zhang F, Wei K, Baglaenko Y, Brenner M, Loh PR, Raychaudhuri S. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat. Methods<\/i>, 16<\/b>, 1289\u20131296 (2019).","DOI":"10.1038\/s41592-019-0619-0"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19) Hao Y, Stuart T, Kowalski MH, Choudhary S, Hoffman P, Hartman A, Srivastava A, Molla G, Madad S, Fernandez-Granda C, Satija R. Dictionary learning for integrative, multimodal and scalable single-cell analysis. Nat. Biotechnol.<\/i>, 42<\/b>, 293\u2013304 (2024).","DOI":"10.1038\/s41587-023-01767-y"},{"key":"20","unstructured":"20) Uhl\u00e9n M, Karlsson MJ, Hober A, et al<\/i>. The human secretome. Sci. Signal.<\/i>, 12<\/b>, eaaz0274 (2019)."},{"key":"21","doi-asserted-by":"crossref","unstructured":"21) Jin S, Plikus MV, Nie Q. CellChat for systematic analysis of cell\u2013cell communication from single-cell transcriptomics. Nat. Protoc.<\/i>, 20<\/b>, 180\u2013219 (2025).","DOI":"10.1038\/s41596-024-01045-4"},{"key":"22","unstructured":"22) Akbani R, Akdemir KC, Aksoy BA, et al<\/i>. Genomic classification of cutaneous melanoma. Cell<\/i>, 161<\/b>, 1681\u20131696 (2015)."},{"key":"23","doi-asserted-by":"crossref","unstructured":"23) Colaprico A, Silva TC, Olsen C, Garofano L, Cava C, Garolini D, Sabedot TS, Malta TM, Pagnotta SM, Castiglioni I, Ceccarelli M, Bontempi G, Noushmehr H. TCGAbiolinks: an R\/Bioconductor package for integrative analysis of TCGA data. Nucleic Acids Res.<\/i>, 44<\/b>, e71 (2016).","DOI":"10.1093\/nar\/gkv1507"},{"key":"24","unstructured":"24) Liu J, Lichtenberg T, Hoadley KA, Poisson LM, Lazar AJ, Cherniack AD, Kovatich AJ, Benz CC, Levine DA, Lee AV, Omberg L, Wolf DM, Shriver CD, Thorsson V, Hu H. An integrated TCGA Pan-Cancer Clinical Data Resource to drive high-quality survival outcome analytics. Cell<\/i>, 173<\/b>, 400\u2013416.e11 (2018)."},{"key":"25","doi-asserted-by":"crossref","unstructured":"25) Goldman MJ, Craft B, Hastie M, Repe\u010dka K, McDade F, Kamath A, Banerjee A, Luo Y, Rogers D, Brooks AN, Zhu J, Haussler D. Visualizing and interpreting cancer genomics data via<\/i> the Xena platform. Nat. Biotechnol.<\/i>, 38<\/b>, 675\u2013678 (2020).","DOI":"10.1038\/s41587-020-0546-8"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26) Forsthuber A, Aschenbrenner B, Korosec A, et al<\/i>. Cancer-associated fibroblast subtypes modulate the tumor-immune microenvironment and are associated with skin cancer malignancy. Nat. Commun.<\/i>, 15<\/b>, 9678 (2024).","DOI":"10.1038\/s41467-024-53908-9"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27) Davis S, Meltzer PS. GEOquery: a bridge between the Gene Expression Omnibus (GEO) and BioConductor. Bioinformatics<\/i>, 23<\/b>, 1846\u20131847 (2007).","DOI":"10.1093\/bioinformatics\/btm254"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28) Meeth K, Wang JX, Micevic G, Damsky W, Bosenberg MW. The YUMM lines: a series of congenic mouse melanoma cell lines with defined genetic alterations. Pigment Cell Melanoma Res.<\/i>, 29<\/b>, 590\u2013597 (2016).","DOI":"10.1111\/pcmr.12498"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29) Kaur A, Ecker BL, Douglass SM, et al<\/i>. Remodeling of the collagen matrix in aging skin promotes melanoma metastasis and affects immune cell motility. Cancer Discov.<\/i>, 9<\/b>, 64\u201381 (2019).","DOI":"10.1158\/2159-8290.CD-18-0193"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30) Zhang Y, Wang T-W, Tamatani M, Zeng X, Nakamura L, Omori S, Yamaguchi K, Hatakeyama S, Shimizu E, Yamazaki S, Furukawa Y, Imoto S, Johmura Y, Nakanishi M. Signaling networks in cancer stromal senescent cells establish malignant microenvironment. Proc. Natl. Acad. Sci. U.S.A.<\/i>, 122<\/b>, e2412818122 (2025).","DOI":"10.1073\/pnas.2412818122"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31) Debby-Brafman A, Burstyn-Cohen T, Klar A, Kalcheim C. F-Spondin, expressed in somite regions avoided by neural crest cells, mediates inhibition of distinct somite domains to neural crest migration. Neuron<\/i>, 22<\/b>, 475\u2013488 (1999).","DOI":"10.1016\/S0896-6273(00)80703-5"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32) Whately KM, Sengottuvel N, Edatt L, Srivastava S, Woods AT, Tsai YS, Porrello A, Zimmerman MP, Chack AC, Jefferys SR, Yacovone G, Kim DJ, Dudley AC, Amelio AL, Pecot CV. Spon1+<\/sup> inflammatory monocytes promote collagen remodeling and lung cancer metastasis through lipoprotein receptor 8 signaling. JCI Insight<\/i>, 9<\/b>, e168792 (2024).","DOI":"10.1172\/jci.insight.168792"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33) Miyakawa R, Kobayashi M, Sugimoto K, Endo Y, Kojima M, Kobayashi Y, Furukawa S, Honda T, Watanabe T, Asano S, Soeda S, Hashimoto Y, Fujimori K, Chiba H. SPON1 is an independent prognostic biomarker for ovarian cancer. J. Ovarian Res.<\/i>, 16<\/b>, 95 (2023).","DOI":"10.1186\/s13048-023-01180-8"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34) Terai Y, Abe M, Miyamoto K, Koike M, Yamasaki M, Ueda M, Ueki M, Sato Y. Vascular smooth muscle cell growth-promoting factor\/F-spondin inhibits angiogenesis via<\/i> the blockade of integrin \u03b1v\u03b23 on vascular endothelial cells. J. Cell. Physiol.<\/i>, 188<\/b>, 394\u2013402 (2001).","DOI":"10.1002\/jcp.1122"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35) Del Mistro G, Riemann S, Schindler S, Beissert S, Kontermann RE, Ginolhac A, Halder R, Presta L, Sinkkonen L, Sauter T, Kulms D. Focal adhesion kinase plays a dual role in TRAIL resistance and metastatic outgrowth of malignant melanoma. Cell Death Dis.<\/i>, 13<\/b>, 54 (2022).","DOI":"10.1038\/s41419-022-04502-8"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36) Chang H, Dong T, Ma X, Zhang T, Chen Z, Yang Z, Zhang Y. Spondin 1 promotes metastatic progression through Fak and Src dependent pathway in human osteosarcoma. Biochem. Biophys. Res. Commun.<\/i>, 464<\/b>, 45\u201350 (2015).","DOI":"10.1016\/j.bbrc.2015.05.092"},{"key":"37","doi-asserted-by":"crossref","unstructured":"37) Horton JD, Cohen JC, Hobbs HH. Molecular biology of PCSK9: its role in LDL metabolism. Trends Biochem. Sci.<\/i>, 32<\/b>, 71\u201377 (2007).","DOI":"10.1016\/j.tibs.2006.12.008"},{"key":"38","doi-asserted-by":"crossref","unstructured":"38) Seidah NG, Benjannet S, Wickham L, Marcinkiewicz J, Jasmin SB, Stifani S, Basak A, Prat A, Chr\u00e9tien M. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): Liver regeneration and neuronal differentiation. Proc. Natl. Acad. Sci. U.S.A.<\/i>, 100<\/b>, 928\u2013933 (2003).","DOI":"10.1073\/pnas.0335507100"},{"key":"39","unstructured":"39) Watanabe H, Takehana K, Date M, Shinozaki T, Raz A. Tumor cell autocrine motility factor is the neuroleukin\/phosphohexose isomerase polypeptide. Cancer Res.<\/i>, 56<\/b>, 2960\u20132963 (1996)."},{"key":"40","doi-asserted-by":"crossref","unstructured":"40) Jeffery CJ. Moonlighting proteins. Trends Biochem. Sci.<\/i>, 24<\/b>, 8\u201311 (1999).","DOI":"10.1016\/S0968-0004(98)01335-8"},{"key":"41","doi-asserted-by":"crossref","unstructured":"41) Chaib S, Tchkonia T, Kirkland JL. Cellular senescence and senolytics: the path to the clinic. Nat. 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