Epigenomic analyses identify FOXM1 as a key regulator of anti-tumor immune response in esophageal adenocarcinoma.
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
19 Feb 2024
19 Feb 2024
Historique:
received:
26
07
2023
accepted:
22
01
2024
revised:
18
01
2024
medline:
20
2
2024
pubmed:
20
2
2024
entrez:
19
2
2024
Statut:
epublish
Résumé
Unlike most cancer types, the incidence of esophageal adenocarcinoma (EAC) has rapidly escalated in the western world over recent decades. Using whole genome bisulfite sequencing (WGBS), we identify the transcription factor (TF) FOXM1 as an important epigenetic regulator of EAC. FOXM1 plays a critical role in cellular proliferation and tumor growth in EAC patient-derived organoids and cell line models. We identify ERBB2 as an upstream regulator of the expression and transcriptional activity of FOXM1. Unexpectedly, gene set enrichment analysis (GSEA) unbiased screen reveals a prominent anti-correlation between FOXM1 and immune response pathways. Indeed, syngeneic mouse models show that FOXM1 inhibits the infiltration of CD8
Identifiants
pubmed: 38373993
doi: 10.1038/s41419-024-06488-x
pii: 10.1038/s41419-024-06488-x
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
152Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : R37CA237022
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : R37CA237022
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : R37CA237022
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : R37CA237022
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : R37CA237022
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : R37CA237022
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : R37CA237022
Informations de copyright
© 2024. The Author(s).
Références
Chien C-R, Lin C-Y, Chen C-Y. Re: Incidence of adenocarcinoma of the esophagus among white Americans by sex, stage, and age. J Natl Cancer Inst. 2009;101:1428.
pubmed: 19724025
doi: 10.1093/jnci/djp304
Mayer R. Esophageal cancer. Harrisons Princ Intern Med. 2007;15:578–9.
Siegal R, Miller K, Jemal A. Cancer statistics, 2012. Ca Cancer J Clin. 2014;64:9–29.
Zhao JJ, Yap DWT, Chan YH, Tan BKJ, Teo CB, Syn NL, et al. Low programmed death-ligand 1–expressing subgroup outcomes of first-line immune checkpoint inhibitors in gastric or esophageal adenocarcinoma. J Clin Oncol. 2022;40:392–402.
pubmed: 34860570
doi: 10.1200/JCO.21.01862
Sharma P, Hu-Lieskovan S, Wargo J, Ribas A. Leading edge review primary, adaptive, and acquired resistance to cancer immunotherapy. Cell. 2017;168:707–23.
pubmed: 28187290
pmcid: 5391692
doi: 10.1016/j.cell.2017.01.017
Sharma P, Siddiqui BA, Anandhan S, Yadav SS, Subudhi SK, Gao J, et al. The next decade of immune checkpoint therapy. Cancer Discov. 2021;11:838–57.
pubmed: 33811120
doi: 10.1158/2159-8290.CD-20-1680
Ladányi A, Sebestyén T, Balatoni T, Varga A, Oláh J, Liszkay G. 524 Tumor-infiltrating immune cells as potential biomarkers predicting response to treatment and survival in patients with metastatic melanoma receiving ipilimumab therapy. Eur J Cancer. 2015;3:S111–S2.
doi: 10.1016/S0959-8049(16)30325-2
Zheng L, Qin S, Si W, Wang A, Xing B, Gao R, et al. Pan-cancer single-cell landscape of tumor-infiltrating T cells. Science. 2021;374:abe6474.
pubmed: 34914499
doi: 10.1126/science.abe6474
Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515:568–71.
pubmed: 25428505
pmcid: 4246418
doi: 10.1038/nature13954
Zheng Y, Ziman B, Ho AS, Sinha UK, Xu L-Y, Li E-M, et al. Comprehensive analyses of partially methylated domains and differentially methylated regions in esophageal cancer reveal both cell-type-and cancer-specific epigenetic regulation. Genome Biol. 2023;24:193.
pubmed: 37620896
pmcid: 10463844
doi: 10.1186/s13059-023-03035-3
Lin CY, Erkek S, Tong Y, Yin L, Federation AJ, Zapatka M, et al. Active medulloblastoma enhancers reveal subgroup-specific cellular origins. Nature. 2016;530:57–62.
pubmed: 26814967
pmcid: 5168934
doi: 10.1038/nature16546
Hovestadt V, Jones DT, Picelli S, Wang W, Kool M, Northcott PA, et al. Decoding the regulatory landscape of medulloblastoma using DNA methylation sequencing. Nature. 2014;510:537–41.
pubmed: 24847876
doi: 10.1038/nature13268
Pan J, Silva TC, Gull N, Yang Q, Plummer JT, Chen S, et al. Lineage-specific epigenomic and genomic activation of oncogene HNF4A promotes gastrointestinal adenocarcinomas. Cancer Res. 2020;80:2722–36.
pubmed: 32332020
doi: 10.1158/0008-5472.CAN-20-0390
Yao L, Shen H, Laird PW, Farnham PJ, Berman BP. Inferring regulatory element landscapes and transcription factor networks from cancer methylomes. Genome Biol. 2015;16:1–21.
doi: 10.1186/s13059-015-0668-3
Silva TC, Coetzee SG, Gull N, Yao L, Hazelett DJ, Noushmehr H, et al. ELMER v. 2: an R/Bioconductor package to reconstruct gene regulatory networks from DNA methylation and transcriptome profiles. Bioinformatics. 2019;35:1974–7.
pubmed: 30364927
doi: 10.1093/bioinformatics/bty902
Network CGAA. The chromatin accessibility landscape of primary human cancers. Science. 2018;362:6413.
Network CGAR. Integrated genomic characterization of oesophageal carcinoma. Nature. 2017;541:169.
doi: 10.1038/nature20805
Keld R, Guo B, Downey P, Gulmann C, Ang YS, Sharrocks AD. The ERK MAP kinase-PEA3/ETV4-MMP-1 axis is operative in oesophageal adenocarcinoma. Mol Cancer. 2010;9:1–14.
doi: 10.1186/1476-4598-9-313
Nowicki-Osuch K, Zhuang L, Jammula S, Bleaney CW, Mahbubani KT, Devonshire G, et al. Molecular phenotyping reveals the identity of Barrett’s esophagus and its malignant transition. Science. 2021;373:760–7.
pubmed: 34385390
doi: 10.1126/science.abd1449
Zhao H, Cheng Y, Kalra A, Ma K, Zheng Y, Ziman B, et al. Generation and multiomic profiling of a TP53/CDKN2A double-knockout gastroesophageal junction organoid model. Sci Transl Med. 2022;14:eabq6146.
pubmed: 36449602
pmcid: 10026384
doi: 10.1126/scitranslmed.abq6146
Li X, Francies HE, Secrier M, Perner J, Miremadi A, Galeano-Dalmau N, et al. Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics. Nat Commun. 2018;9:2983.
pubmed: 30061675
pmcid: 6065407
doi: 10.1038/s41467-018-05190-9
Chen L, Huang M, Plummer J, Pan J, Jiang YY, Yang Q, et al. Master transcription factors form interconnected circuitry and orchestrate transcriptional networks in oesophageal adenocarcinoma. Gut. 2020;69:630–40.
pubmed: 31409603
doi: 10.1136/gutjnl-2019-318325
Wiseman EF, Chen X, Han N, Webber A, Ji Z, Sharrocks AD, et al. Deregulation of the FOXM1 target gene network and its coregulatory partners in oesophageal adenocarcinoma. Mol Cancer. 2015;14:1–14.
doi: 10.1186/s12943-015-0339-8
Yamamoto M, Nomura S, Hosoi A, Nagaoka K, Iino T, Yasuda T, et al. Established gastric cancer cell lines transplantable into C57 BL/6 mice show fibroblast growth factor receptor 4 promotion of tumor growth. Cancer Sci. 2018;109:1480–92.
pubmed: 29532565
pmcid: 5980194
doi: 10.1111/cas.13569
Quante M, Wang TC, Bass AJ. Adenocarcinoma of the oesophagus: is it gastric cancer? Gut. 2023;72:1027–9.
pubmed: 35365571
doi: 10.1136/gutjnl-2022-327096
Network CGAR. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513:202.
doi: 10.1038/nature13480
Li T, Fu J, Zeng Z, Cohen D, Li J, Chen Q, et al. TIMER2. 0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res. 2020;48:W509–W14.
pubmed: 32442275
pmcid: 7319575
doi: 10.1093/nar/gkaa407
Franciszkiewicz K, Boissonnas A, Boutet M, Combadiere C, Mami-Chouaib F. Role of chemokines and chemokine receptors in shaping the effector phase of the antitumor immune response. Cancer Res. 2012;72:6325–32.
pubmed: 23222302
doi: 10.1158/0008-5472.CAN-12-2027
Tokunaga R, Zhang W, Naseem M, Puccini A, Berger MD, Soni S, et al. CXCL9, CXCL10, CXCL11/CXCR3 axis for immune activation–a target for novel cancer therapy. Cancer Treat Rev. 2018;63:40–7.
pubmed: 29207310
doi: 10.1016/j.ctrv.2017.11.007
Jhunjhunwala S, Hammer C, Delamarre L. Antigen presentation in cancer: insights into tumour immunogenicity and immune evasion. Nat Rev Cancer. 2021;21:298–312.
pubmed: 33750922
doi: 10.1038/s41568-021-00339-z
Harlin H, Meng Y, Peterson AC, Zha Y, Tretiakova M, Slingluff C, et al. Chemokine expression in melanoma metastases associated with CD8+ T-cell recruitment. Cancer Res. 2009;69:3077–85.
pubmed: 19293190
doi: 10.1158/0008-5472.CAN-08-2281
Hopewell EL, Zhao W, Fulp WJ, Bronk CC, Lopez AS, Massengill M, et al. Lung tumor NF-κB signaling promotes T cell-mediated immune surveillance. J Clin Investig. 2013;123:2509–22.
pubmed: 23635779
pmcid: 3668836
doi: 10.1172/JCI67250
Hogquist KA, Jameson SC, Heath WR, Howard JL, Bevan MJ, Carbone FR. T cell receptor antagonist peptides induce positive selection. Cell. 1994;76:17–27.
pubmed: 8287475
doi: 10.1016/0092-8674(94)90169-4
Tang Q, Liu C, Zhang S, He L, Liu Y, Wang J, et al. FOXM1 increases hTERT protein stability and indicates poor prognosis in gastric cancer. Neoplasia. 2023;36:100863.
pubmed: 36528911
doi: 10.1016/j.neo.2022.100863
Laissue P. The forkhead-box family of transcription factors: key molecular players in colorectal cancer pathogenesis. Mol Cancer. 2019;18:5.
pubmed: 30621735
pmcid: 6325735
doi: 10.1186/s12943-019-0938-x
Xie D, Yu S, Li L, Quan M, Gao Y. The FOXM1/ATX signaling contributes to pancreatic cancer development. Am J Transl Res. 2020;12:4478.
pubmed: 32913521
pmcid: 7476150
Goltsov AA, Fang B, Pandita TK, Maru DM, Swisher SG, Hofstetter WL. HER2 confers resistance to foretinib inhibition of MET-amplified esophageal adenocarcinoma cells. Ann Thorac Surg. 2018;105:363–70.
pubmed: 29223420
doi: 10.1016/j.athoracsur.2017.09.003
Janjigian YY, Ku GY, Ilson DH, Boyar MS, Capanu M, Chou JF, et al. A phase II study of afatinib in patients (pts) with metastatic human epidermal growth factor receptor (HER2)-positive trastuzumab refractory esophagogastric (EG) cancer. American Society of Clinical Oncology; 2015.
Barbuti AM, Zhang G-N, Gupta P, Narayanan S, Chen Z-S. EGFR and HER2 inhibitors as sensitizing agents for cancer chemotherapy. Protein kinase inhibitors as sensitizing agents for chemotherapy. Elsevier; 2019. pp 1–11.
Almhanna K, Rosa M, Henderson-Jackson E, Jiang K, Shamekh R, Sayegh Z, et al. Her-2 expression in gastroesophageal intestinal metaplasia, dysplasia, and adenocarcinoma. Appl Immunohistochem Mol Morphol. 2016;24:633.
pubmed: 26186253
pmcid: 7771552
doi: 10.1097/PAI.0000000000000243
Shah MA, Kennedy EB, Alarcon-Rozas AE, Alcindor T, Bartley AN, Malowany AB, et al. Immunotherapy and targeted therapy for advanced gastroesophageal cancer: ASCO guideline. J Clin Oncol. 2023;41:1470–91.
pubmed: 36603169
doi: 10.1200/JCO.22.02331
Miao L, Xiong X, Lin Y, Cheng Y, Lu J, Zhang J, et al. Down-regulation of FoxM1 leads to the inhibition of the epithelial-mesenchymal transition in gastric cancer cells. Cancer Genet. 2014;207:75–82.
pubmed: 24726291
doi: 10.1016/j.cancergen.2014.02.008
Dibb M, Han N, Choudhury J, Hayes S, Valentine H, West C, et al. The FOXM1-PLK1 axis is commonly upregulated in oesophageal adenocarcinoma. Br J Cancer. 2012;107:1766–75.
pubmed: 23037713
pmcid: 3493860
doi: 10.1038/bjc.2012.424
Madhi H, Lee JS, Choi YE, Li Y, Kim MH, Choi Y, et al. FOXM1 inhibition enhances the therapeutic outcome of lung cancer immunotherapy by modulating PD‐L1 expression and cell proliferation. Adv Sci. 2022;9:2202702.
doi: 10.1002/advs.202202702
Ai C, Zhang J, Lian S, Ma J, Győrffy B, Qian Z, et al. FOXM1 functions collaboratively with PLAU to promote gastric cancer progression. J Cancer. 2020;11:788.
pubmed: 31949481
pmcid: 6959008
doi: 10.7150/jca.37323
Jiang Y-Y, Jiang Y, Li C-Q, Zhang Y, Dakle P, Kaur H, et al. TP63, SOX2, and KLF5 establish a core regulatory circuitry that controls epigenetic and transcription patterns in esophageal squamous cell carcinoma cell lines. Gastroenterology. 2020;159:1311–27. e19.
pubmed: 32619460
doi: 10.1053/j.gastro.2020.06.050
Ziman B, Oviedo NJ. Measuring protein levels in planarians using western blotting. STAR Protoc. 2021;2:100274.
pubmed: 33490988
pmcid: 7811048
doi: 10.1016/j.xpro.2020.100274
Rogerson C, Ogden S, Britton E, Consortium O, Ang Y, Sharrocks AD. Repurposing of KLF5 activates a cell cycle signature during the progression from a precursor state to oesophageal adenocarcinoma. Elife 2020;9:e57189.
pubmed: 32880368
pmcid: 7544504
doi: 10.7554/eLife.57189
Kumar S, Stecher G, Tamura K. MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol Biol Evol. 2016;33:1870–4.
pubmed: 27004904
pmcid: 8210823
doi: 10.1093/molbev/msw054
Ramírez F, Ryan DP, Grüning B, Bhardwaj V, Kilpert F, Richter A. deepTools2: a next generation web server for deep-sequencing data analysis. Nucleic Acids Res. 2016;44:W160.
Mesirov JP. Integrative genomics viewer. Nat Biotechnol. 2011;29:24–6.
pubmed: 21221095
pmcid: 3346182
doi: 10.1038/nbt.1754