Cited by 118Pancreatic and Hepatic Oncology ResearchCancer Genomics and DiagnosticsCancer Cells and Metastasis

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Cell of Origin Influences Pancreatic Cancer Subtype

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Flowers, Brittany M., Xu, Hang, Mulligan, Abigail S., Hanson, Kathryn J., Seoane, Jose A., Vogel, Hannes, Curtis, Christina, Wood, Laura D., Attardi, Laura D.·2021·Cancer Discovery

DOI 10.1158/2159-8290.cd-20-0633PMC PMC8134763

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with a 5-year survival rate of approximately 9%. An improved understanding of PDAC initiation and progression is paramount for discovering strategies to better detect and combat this disease. Although transcriptomic analyses have uncovered distinct molecular subtypes of human PDAC, the factors that influence subtype development remain unclear. Here, we interrogate the impact of cell of origin and different Trp53 alleles on tumor evolution, using a panel of tractable genetically engineered mouse models. Oncogenic KRAS expression, coupled with Trp53 deletion or point mutation, drives PDAC from both acinar and ductal cells. Gene-expression analysis reveals further that ductal cell–derived and acinar cell–derived tumor signatures are enriched in basal-like and classical subtypes of human PDAC, respectively. These findings highlight cell of origin as one factor that influences PDAC molecular subtypes and provide insight into the fundamental impact that the very earliest events in carcinogenesis can have on cancer evolution. Significance: Although human PDAC has been classified into different molecular subtypes, the etiology of these distinct subtypes remains unclear. Using mouse genetics, we reveal that cell of origin is an important determinant of PDAC molecular subtype. Deciphering the biology underlying pancreatic cancer subtypes may reveal meaningful distinctions that could improve clinical intervention. This article is highlighted in the In This Issue feature, p. 521

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Cancer statistics, 2020
Siegel, R. L., Miller, K. D., & Jemal, A. (2020) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21590 · Cited by 20,444
GSVA: gene set variation analysis for microarray and RNA-Seq data
Hänzelmann, S., Castelo, R., & Guinney, J. (2013) · BMC Bioinformatics · doi:10.1186/1471-2105-14-7 · Cited by 15,440
Projecting Cancer Incidence and Deaths to 2030: The Unexpected Burden of Thyroid, Liver, and Pancreas Cancers in the United States
Rahib, L., Smith, B. D., Aizenberg, R., Rosenzweig, A. B., Fleshman, J. M., & Matrisian, L. M. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-0155 · Cited by 7,094
Genomic analyses identify molecular subtypes of pancreatic cancer
Bailey, P., Chang, D. K., Nones, K., Johns, A. L., Patch, A.-M., Gingras, M.-C., Miller, D. K., Christ, A. N., Bruxner, T. J. C., Quinn, M. C., et al. (2016) · Nature · doi:10.1038/nature16965 · Cited by 3,621 · cited 6×
“We used publicly available gene expression and clinical data for the ICGC Australian (13), ICGC Canadian (PACA-CA, downloaded from the ICGC data portal – https://dcc.”
BackgroundMethodResultInfluential
Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris
The Tabula Muris Consortium, coordination, O., coordination, L., processing, O. C. A., sequencing, L. P. A., analysis, C. D., annotation, C. T., Writing group, Supplemental text writing group, & Principal investigators (2018) · Nature · doi:10.1038/s41586-018-0590-4 · Cited by 2,842
Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice
Hingorani, S. R., Wang, L., Multani, A. S., Combs, C., Deramaudt, T. B., Hruban, R. H., Rustgi, A. K., Chang, S., & Tuveson, D. A. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.04.023 · Cited by 2,609
Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse
Hingorani, S. R., Petricoin, E. F., Maitra, A., Rajapakse, V., King, C., Jacobetz, M. A., Ross, S., Conrads, T. P., Veenstra, T. D., Hitt, B. A., et al. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00309-x · Cited by 2,471
Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma
Moffitt, R. A., Marayati, R., Flate, E. L., Volmar, K. E., Loeza, S. G. H., Hoadley, K. A., Rashid, N. U., Williams, L. A., Eaton, S. C., Chung, A. H., et al. (2015) · Nature Genetics · doi:10.1038/ng.3398 · Cited by 2,194
Integrated genomic characterization of pancreatic ductal adenocarcinoma
Raphael, B. J., Hruban, R. H., Aguirre, A. J., Moffitt, R. A., Yeh, J. J., Stewart, C., Robertson, A. G., Cherniack, A. D., Gupta, M., Getz, G., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.07.007 · Cited by 2,019
Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy
Collisson, E. A., Sadanandam, A., Olson, P., Gibb, W. J., Truitt, M., Gu, S., Cooc, J., Weinkle, J., Kim, G. E., Jakkula, L., et al. (2011) · Nature Medicine · doi:10.1038/nm.2344 · Cited by 1,967

Show all 52 references

Research works printed but not linked: 1

Gidekel Friedlander, 2009, Context-dependent transformation of adult pancreatic cells by oncogenic K-Ras, Cancer Cell, 16, 379, 10.1016/j.ccr.2009.09.027 · DOI

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Mayerle, J. V. (2022) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-022-00595-w · Cited by 5
A triple hormone receptor ER, AR, and VDR signature is a robust prognosis predictor in breast cancer
Omar, M., Harrell, J. C., Tamimi, R. M., Marchionni, L., Erdoğan, C., Nakshatri, H., & Ince, T. A. (2024) · Breast Cancer Research · doi:10.1186/s13058-024-01876-9 · Cited by 4
Brusatol increases chemotherapeutic drug efficacy in pancreatic ductal adenocarcinoma by suppressing Nrf2 signaling
Zhang, J., Xu, H., Wu, Y., Cho, W. C. S., Li, Y., Ren, P., Xian, Y., & Lin, Z. (2024) · Acta Materia Medica · doi:10.15212/amm-2024-0016 · Cited by 4
Self-citation
Biotechnological advances in 3D modeling of cancer initiation. Examples from pancreatic cancer research and beyond
Handschin, C., Shalhoub, H., Mazet, A., Guyon, C., Dusserre, N., Boutet-Robinet, E. A., Oliveira, H., & Guillermet‐Guibert, J. (2025) · Biofabrication · doi:10.1088/1758-5090/adb51c · Cited by 5
The recombinant defensin/HSA fusion protein that inhibits NF-κb associated with intensive macropinocytosis shows potent efficacy against pancreatic cancer
Du, Y., Wang, X., Liu, X., Li, Y., Miao, Q., Jiang, M., Sheng, W., & Zhen, Y. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.115057 · Cited by 4
Pancreatic Cancer Ductal Cell of Origin Drives CD73-Dependent Generation of Immunosuppressive AdenosinePreprint
Singh, K., Faraoni, E. Y., Dai, Y., Chandra, V., Vucic, E., Mills, T., Pruski, M. A., Clark, T., Buren, G. V., Thosani, N. C., et al. (2021) · SSRN Electronic Journal · doi:10.1101/2021.11.29.470415 · Cited by 4
Loss of p53 tumor suppression function drives invasion and genomic instability in models of murine pancreatic cancerPreprint
Tonelli, C., Deschênes, A., Yao, M. A., Park, Y., & Tuveson, D. A. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.12.31.472823 · Cited by 4
CD73 Is a Critical Immune Checkpoint in a Molecular Subtype of Pancreatic Cancer
DelGiorno, K. E. (2023) · Cancer Research · doi:10.1158/0008-5472.can-23-0268 · Cited by 4
Integrated single cell RNA sequencing and flow cytometry analysis identifies elevated S100A6+ and S100A8+ myeloid subsets in pancreatic ductal adenocarcinoma
Derakhshani, A., Fonte, R., Porcelli, L., Orang, F. N., Shadbad, M. A., Feriz, A. M., Safarpour, H., Dufour, A., Baradaran, B., Calabrese, A., et al. (2026) · Clinical Immunology · doi:10.1016/j.clim.2026.110665 · Cited by 3
Organoids in the research of pancreatic neoplasms: cultivation, applications, and limitations
Du, C., Liu, Y., Lu, X., Zhang, M., Jiang, S., Cao, Z., Yang, G., Qiu, J., Zhang, T., & Zhao, Y. (2025) · Cancer Letters · doi:10.1016/j.canlet.2025.217968 · Cited by 3
Unraveling dedifferentiation and metastasis traces in pancreatic ductal adenocarcinoma ductal cells: Insights from single-cell RNA sequencing analysis of ITGB4 and C19orf33
Asadzadeh, Z., Hemmat, N., Hassanian, H., Alizadeh, N., Mokhtarzadeh, A., Jafarlou, M., & Baradaran, B. (2023) · Pathology - Research and Practice · doi:10.1016/j.prp.2023.155012 · Cited by 3
Exocrine Pancreas
Wallig, M. A., Vahle, J. L., & Sullivan, J. M. (2024) · Elsevier eBooks · doi:10.1016/b978-0-12-821046-8.00008-6 · Cited by 3
Unveiling the impact of OVOL1 on prognosis, immune microenvironment, and proliferation in pancreatic cancer
Li, J. W., Deng, Z., Yan, Z., Huang, S., Jin, J., Xie, C., & Gan, J. (2025) · Scientific Reports · doi:10.1038/s41598-025-13196-9 · Cited by 2
A cell-state axis underlying colonization in carcinomas with implications for metastasis risk prediction and interception
Handler, J. S., Li, Z., Dveirin, R. K., Lin, J., Fang, W., Wu, S., Forsmo, J. E., Goodarzi, H., Fertig, E. J., & Kalhor, R. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116701 · Cited by 3
LY6D identifies persistent stem-like cells driving pancreatic tumourigenesis
Shi, J., Wang, X., Tang, Y., Meng, S., Zhang, Z., Lu, P., Xu, J., Yu, F., Wang, X., Wang, Z., et al. (2026) · Gut · doi:10.1136/gutjnl-2025-336460 · Cited by 2
Association between cancer genes and germ layer specificity
Lee, H., Lee, S., Cho, W. J., Shin, M., & Park, L. (2022) · Medical Oncology · doi:10.1007/s12032-022-01823-8 · Cited by 2
Road Map to Defeat Pancreatic Cancer
Ferguson, L. P., & Tuveson, D. A. (2025) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-060624-044323 · Cited by 2
Unraveling the therapeutic landscape of miRNAs in pancreatic cancer
El‐Moaty, Z. A., Wasef, M. W., Elsayed, Y. A., Shafiq, A. S., Elnagar, M. A., Mohamed, H. R., Elesawyf, A. E., Mageed, S. S. A., Mohammed, O. A., Abdel‐Reheim, M. A., et al. (2025) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-025-04301-w · Cited by 2
Rare, Tightly-Bound, Multi-Cellular Clusters in the Pancreatic Ducts of Adult Mice Function Like Progenitor Cells and Survive and Proliferate After Acinar Cell Injury
Tremblay, J. R., Ortiz, J., Quijano, J. C., Zook, H. N., Erdem, N., LeBon, J. M., Li, W., Jou, K., Tsark, W. M. K., Mann, J. R., et al. (2024) · Stem Cells · doi:10.1093/stmcls/sxae005 · Cited by 2
Fusobacterium nucleatum induces pancreatic cancer cell proliferation and migration by regulating host autocrine and paracrine signalingPreprint
Udayasuryan, B., Nguyen, T. T. D., Umaña, A., Ahmad, R. N., Roberts, L. M., Sobol, P., Jones, S. D., Munson, J. M., Slade, D. J., & Verbridge, S. S. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.11.19.469245 · Cited by 2
Drug-Induced p53 Activation Limits Pancreatic Cancer InitiationPreprint
Twardowski, J. J., Heist, T. I., Soares, Z. G., Berry, E. S., Ruffolo, L. I., Pröschel, C., & Mello, S. S. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.29.595146 · Cited by 2
Ex-Vivo 3D Cellular Models of Pancreatic Ductal Adenocarcinoma
Aćimović, I., Gabrielová, V., Martínková, S., Eid, M., Vlažný, J., Moravčík, P., Hlavsa, J., Moráň, L., Cakmakci, R. C., Staňo, P., et al. (2024) · Pancreas · doi:10.1097/mpa.0000000000002393 · Cited by 1
Lfng-expressing centroacinar cell is a unique cell-of-origin for p53 deficient pancreatic cancer
Chung, W.-C., Zhang, S., Atfi, A., & Xu, K. (2024) · Oncogene · doi:10.1038/s41388-024-03226-7 · Cited by 1
Comparative spatial transcriptomics of pancreatic cancer with ductal and acinar origins in mouse models
Cui, M., Bai, J., Chang, X., Xiao, R., Mo, S., Soares, K. C., Yang, S., You, L., Liao, Q., He, J. P., et al. (2025) · Clinical and Translational Medicine · doi:10.1002/ctm2.70416 · Cited by 1
Plakophilin 3 drives acinar cell transformation and promotes cancer initiation and progression in pancreas
Li, X., Fang, W., Jiang, T., Zhang, L., Sun, Q., Jiang, H., Guo, F., Ren, H., Zheng, W., Shen, X., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116487 · Cited by 1
Early cellular plasticity promotes progression and dissemination in pancreatic adenocarcinoma
Innamorati, G., Malpeli, G., Giacomello, L., Salvia, R., & Wilkie, T. M. (2026) · Cancer and Metastasis Reviews · doi:10.1007/s10555-026-10326-1 · Cited by 1
A shifting adversary: control of pancreatic cancer transcriptomic subtypes
David, C. J. (2022) · Journal of Cancer Metastasis and Treatment · doi:10.20517/2394-4722.2022.71 · Cited by 1
Towards a Synthesis of the Non-Genetic and Genetic Views of Cancer in Understanding Pancreatic Ductal Adenocarcinoma Initiation and Prevention
Gopalan, V., & Hannenhalli, S. S. (2023) · Cancers · doi:10.3390/cancers15072159 · Cited by 1
[Heterogeneity analysis of pancreatic cancer and identification of molecular subtypes of tumor cells based on CEACAM5, LGALS1 and CENPF gene expression].
Sun, J., Lu, P., Guan, S., & Liu, S. (2023) · PubMed Central · doi:10.12122/j.issn.1673-4254.2023.09.14 · Cited by 1
From Tissue Turnover to the Cell of Origin of Pancreatic Cancer
Kong, B., Thoma, E., & Michalski, C. W. (2023) · doi:10.1002/9781119876007.ch120 · Cited by 1
Participação da ferroptose na morte celular desencadeada pela terapia fotodinâmica com o azul de metileno em adenocarcinoma de ducto pancreático humano
de Almeida, D. R. Q. (2022) · doi:10.11606/t.46.2022.tde-09082023-175313 · Cited by 1
Data from CD73-Dependent Adenosine Signaling through Adora2b Drives Immunosuppression in Ductal Pancreatic Cancer
Faraoni, E. Y., Singh, K., Chandra, V., Roux, O. L., Dai, Y., Şahin, İ., O’Brien, B. J., Strickland, L. N., Li, L., Vucic, E., et al. (2023) · doi:10.1158/0008-5472.c.6487377

Authors: Flowers, B. M., Xu, H., Mulligan, A. S., Hanson, K. J., Seoane, J. A., Vogel, H., Curtis, C., Wood, L. D., & Attardi, L. D.
Affiliations: Stanford Medicine (US)
2Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California.
Johns Hopkins University (US)
Corresponding author: Attardi, Laura D.
ORCID: Flowers, Brittany M.
Xu, Hang
Mulligan, Abigail S.
Hanson, Kathryn J.
Seoane, Jose A.
Vogel, Hannes
Curtis, Christina
Wood, Laura D.
Attardi, Laura D.
Venue: Cancer Discovery
Publisher: American Association for Cancer Research (AACR)
Published: 2021-03-01
Volume: 11
Issue: 3
Pages: 660-677
ISSN: 2159-8274 (ISSN-L)
2159-8290
DOI: 10.1158/2159-8290.cd-20-0633
PMC: PMC8134763
OpenAlex: W3135319098
Cited by: 118
References: 52
Citations by year: 2026: 14 · 2025: 26 · 2024: 26 · 2023: 25 · 2022: 13 · 2021: 14
FWCI: 7.09
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Cancer Discovery (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: NCI R35 (CA197591)
Blavatnik Family Fellowship
NIH Director's Pioneer Award (DP1-CA238296)
Topics: Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords: pancreatic ductal adenocarcinoma, cell of origin, tumor molecular subtypes, Trp53, KRAS, acinar cells, ductal cells, genetically engineered mouse models, basal-like subtype, classical subtype, tumor evolution, carcinogenesis
MeSH terms: Alleles, Animals, Cell Transformation, Neoplastic, Disease Models, Animal, Disease Susceptibility, Humans, Immunohistochemistry, Mutation, Oncogenes, Pancreatic Neoplasms, Prognosis, Biomarkers, Tumor, Gene Expression Regulation, Neoplastic, Proto-Oncogene Proteins p21(ras), Computational Biology, Gene Expression Profiling, Carcinoma, Pancreatic Ductal, Mice, Kaplan-Meier Estimate, Transcriptome, Acinar Cells

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Cell of Origin Influences Pancreatic Cancer Subtype

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