ArticleNature communications2022
A local tumor microenvironment acquired super-enhancer induces an oncogenic driver in colorectal carcinoma.
Erratum issuedOpen access · goldAbstract read
In one paragraph
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 29 papers.
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0cells of the map it votes in
29citing papers in PubMed
3.5field-weighted citation impact, top 6% of its field
What it found
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Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
- From cell to disease: Regulatory networks and mechanisms of super‑enhancers in aging (Review).Molecular medicine reports · 2026Review
- IL-26-driven epigenetic remodeling promotes immune evasion in colorectal cancer.Nature communications · 2026Article
- STED: flexible cross-modal topic modeling infers cell-type-specific regulatory landscapes from bulk epigenomics.Briefings in bioinformatics · 2026Article
- TFAP2C protects against ferroptosis in ovarian cancer through the KEAP1-NRF2 axis by recruiting HDAC1/2.Oncogene · 2026Article
- Molecular mechanisms of KMT2C alterations in gastrointestinal cancers: enhancer network destabilization, lineage plasticity, and clinical translation.Frontiers in immunology · 2026Review
- Epigenetic regulation of PANoptosis: DNA methylation, histone modifications and non-coding RNAs.EXCLI journal · 2026Review
- Organoids glimpse: the nexus for diverse tumor heterogeneity.Frontiers in cell and developmental biology · 2026Review
- Decoding cancer heterogeneity through super-enhancer landscapes: from subtype discovery to therapeutic opportunity.Briefings in bioinformatics · 2025Review
- Enhancer Reprogramming Reveals the Tumorigenic Role of PTPRZ1 in Lung Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Super-enhancer-driven EFNA1 fuels tumor progression in cervical cancer via the FOSL2-Src/AKT/STAT3 axis.The Journal of clinical investigation · 2025Article
- Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies.Cell death discovery · 2025Review
- Super-enhancer DNA methylation in cancer: the mechanism of action and therapeutic directions.Frontiers in oncology · 2025Review
- Article
- Super-Enhancer Driven LIF/LIFR-STAT3-SOX2 Regulatory Feedback Loop Promotes Cancer Stemness in Head and Neck Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Epigenetic reprogramming in gastrointestinal cancer: biology and translational perspectives.MedComm · 2024Review
- DKK1-SE recruits AP1 to activate the target gene DKK1 thereby promoting pancreatic cancer progression.Cell death & disease · 2024Article
- Super-enhancer-driven LIF promotes the mesenchymal transition in glioblastoma by activating ITGB2 signaling feedback in microglia.Neuro-oncology · 2024Article
- TWEAK/Fn14 signalling driven super-enhancer reprogramming promotes pro-metastatic metabolic rewiring in triple-negative breast cancer.Nature communications · 2024Article
- Effects of super-enhancers in cancer metastasis: mechanisms and therapeutic targets.Molecular cancer · 2024Review
- Mediator kinase module proteins, genetic alterations and expression of super-enhancer regulated genes in colorectal cancer.Pharmacological reports : PR · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
27 authors at 5 institutions in 1 country.
Royce W ZhouDepartment of Oncological Sciences, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Jia Xu *Department of Oncological Sciences, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Tiphaine C Martin *Department of Oncological Sciences, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.ORCID http://orcid.org/0000-0001-9990-1455
Alexis L ZachemDepartment of Oncological Sciences, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
John HeDepartment of Oncological Sciences, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Sait OzturkDepartment of Oncological Sciences, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Deniz DemirciogluDepartment of Oncological Sciences, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.ORCID http://orcid.org/0000-0001-7857-0407
Ankita BansalDepartment of Oncological Sciences, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Andrew P TrottaDepartment of Oncological Sciences, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Bruno GiottiDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Berkley GryderDepartment of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, 44106, USA.ORCID http://orcid.org/0000-0003-0130-2302
Yao ShenDepartment of Oncological Sciences, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Xuewei WuDepartment of Oncological Sciences, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Saul CarcamoDepartment of Oncological Sciences, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Kaitlyn BoschDepartment of Oncological Sciences, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Benjamin HopkinsDepartment of Oncological Sciences, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.ORCID http://orcid.org/0000-0002-7970-6430
Alexander TsankovGraduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.ORCID http://orcid.org/0000-0002-7955-4414
Randolph SteinhagenDivision of Colon and Rectal Surgery, Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Drew R JonesMetabolomics Core Resource Laboratory, NYU Langone Health, New York, NY, 10016, USA.
John AsaraMass Spectrometry Core, Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA.
Jerry E ChipukDepartment of Oncological Sciences, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Rachel BrodyMount Sinai Biorepository, Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Steven ItzkowitzDivision of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Iok In Christine ChioInstitute for Cancer Genetics, Department of Genetics and Development, Columbia University Medical Center, New York, NY, 10032, USA.ORCID http://orcid.org/0000-0002-3635-2679
Dan HassonDepartment of Oncological Sciences, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Emily BernsteinDepartment of Oncological Sciences, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.ORCID http://orcid.org/0000-0001-6533-8326
Ramon E ParsonsDepartment of Oncological Sciences, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. ramon.parsons@mssm.edu.ORCID http://orcid.org/0000-0002-6656-3514
Icahn School of Medicine at Mount Sinai · USBeth Israel Deaconess Medical Center · USCase Western Reserve University · USColumbia University Irving Medical Center · USTisch Hospital · US
Funding
THE TISCH CANCER INSTITUTE - CANCER CENTER SUPPORT GRANTP30CA196521 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Ramon E Parsons · 2015 to 2026
$35.4MPTEN and CancerR35CA220491 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI PARSONS, RAMON E · 2017 to 2023
$6.8MDeciphering the tumor suppressive functions of macroH2AR01CA154683 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BERNSTEIN, EMILY · 2011 to 2021
$3.9MChronic Mitochondrial Division and Melanoma: Mechanism, Prognosis, and TherapyR01CA267696 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Jerry Edward Chipuk · 2022 to 2026
$2.4MThe Oncogene Activated Mitochondrial Unfolded Protein Response Regulates Senescence BiologyR01CA271346 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Jerry Edward Chipuk · 2023 to 2026
$2.4MStudying the role of eIF4A in Pancreatic CancerR01CA267870 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Christine Iok In Chio · 2022 to 2026
$2.3MEpigenetic and microenvironmental regulation of dormant disseminated cancerR01CA218024 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AGUIRRE-GHISO, JULIO A. · 2017 to 2021
$2.2MCOVID and Translational Science supercomputer (CATS)S10OD030463 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVATCH, PATRICIA · 2021 to 2021
$2.0MBig Omics Data Engine 2 SupercomputerS10OD026880 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVATCH, PATRICIA · 2019 to 2019
$2.0MFunction and Regulation of the BCL-2 FamilyR01CA237264 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CHIPUK, JERRY EDWARD · 2020 to 2024
$1.9MNRF2-dependent redox signaling in pancreatic cancerR01CA240654 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CHIO, CHRISTINE IOK IN · 2020 to 2024
$1.8M(PQ9) Developing EZH2 Degraders for Treating Triple-Negative Breast CancerR01CA230854 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI JIN, JIAN, PARSONS, RAMON E · 2018 to 2022
$1.5MNCI NIH HHS F30 CA243207NCI NIH HHS P30 CA196521NCI NIH HHS R01 CA154683NCI NIH HHS R01 CA218024NCI NIH HHS R01 CA230854NCI NIH HHS R01 CA237264NCI NIH HHS R01 CA240654NCI NIH HHS R01 CA267696NCI NIH HHS R01 CA267870NCI NIH HHS R01 CA271346NCI NIH HHS R35 CA220491NIH HHS S10 OD026880NIH HHS S10 OD030282NIH HHS S10 OD030463
Abstract
Tumors exhibit enhancer reprogramming compared to normal tissue. The etiology is largely attributed to cell-intrinsic genomic alterations. Here, using freshly resected primary CRC tumors and patient-matched adjacent normal colon, we find divergent epigenetic landscapes between CRC tumors and cell lines. Intriguingly, this phenomenon extends to highly recurrent aberrant super-enhancers gained in CRC over normal. We find one such super-enhancer activated in epithelial cancer cells due to surrounding inflammation in the tumor microenvironment. We restore this super-enhancer and its expressed gene, PDZK1IP1, following treatment with cytokines or xenotransplantation into nude mice, thus demonstrating cell-extrinsic etiology. We demonstrate mechanistically that PDZK1IP1 enhances the reductive capacity CRC cancer cells via the pentose phosphate pathway. We show this activation enables efficient growth under oxidative conditions, challenging the previous notion that PDZK1IP1 acts as a tumor suppressor in CRC. Collectively, these observations highlight the significance of epigenomic profiling on primary specimens.
Indexed as
Colorectal NeoplasmsTumor MicroenvironmentAnimalsCarcinogenesisCell Line, TumorCell ProliferationCytokinesEnhancer Elements, GeneticGene Expression Regulation, NeoplasticMiceMice, NudeCytokines
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