Evidence map›Paper›PMID 42250222›Full record

ArticleCell reports2026

SLC22A3/OCT3 drives serotonin-mediated stemness in pancreatic cancer.

Nivedeta Krishna Kumar, Venkatesh Varadharaj, Neelanjana Gayen, Annant Bir Kaur, Kirtana Arikath, Ashu Shah, Poompozhil Mathivanan, Palanisamy Nallasamy, Zahraa Wajih Alsafwani, Bhuvaneshwari Seshadri and 10 more

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Article in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

20 authors.

Nivedeta Krishna KumarDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Venkatesh VaradharajDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Neelanjana GayenDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Annant Bir KaurDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Kirtana ArikathDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Ashu ShahDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Poompozhil MathivananDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Palanisamy NallasamyDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Zahraa Wajih AlsafwaniDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Bhuvaneshwari SeshadriDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Pratima RautDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Sanchita RauthDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Jimmie PersingerDepartment of Genetics Cell Biology & Anatomy, University of Nebraska Medical Center, Omaha, NE, USA.
Sandipan BrahmaFred and Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center at Omaha, Omaha, NE, USA; Department of Genetics Cell Biology & Anatomy, University of Nebraska Medical Center, Omaha, NE, USA.
Micah SchottDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Fred and Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center at Omaha, Omaha, NE, USA.
Rebecca E Oberley-DeeganDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Fred and Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center at Omaha, Omaha, NE, USA.
Geoffrey A TalmonDepartment of Pathology, Microbiology & Immunology, University of Nebraska Medical Center, Omaha, NE, USA.
Jesse L CoxDepartment of Pathology, Microbiology & Immunology, University of Nebraska Medical Center, Omaha, NE, USA.
Surinder K BatraDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Fred and Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center at Omaha, Omaha, NE, USA. Electronic address: sbatra@unmc.edu.
Moorthy P PonnusamyDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Fred and Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center at Omaha, Omaha, NE, USA. Electronic address: mpalanim@unmc.edu.

Funding

Pancreatic Cancer Detection ConsortiumU01CA210240 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Michael A. Hollingsworth · 2017 to 2026
$12.9M
Validation of biomarkers for risk prediction and early diagnosis of Pancreatic AdenocarcinomaU01CA200466 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Surinder K. Batra, Randall Brand · 2016 to 2026
$11.3M
Project 3: MUC16-Mediated Metabolic Reprograming Induces PC MetastasisP01CA217798 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI THAYER, SARAH P · 2018 to 2022
$8.1M
Truncated O-glycan-dependent mechanisms inducing metastatic dissemination in pancreatic cancerR01CA273349 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., PONNUSAMY, MOORTHY P. · 2022 to 2025
$2.7M
Molecular Imaging Probe(s) for Optical Surgical Navigation of Pancreatic CancerR01CA256973 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Surinder K. Batra, Michael Bouvet · 2022 to 2026
$2.2M
Connectivity mapping identified novel combination therapy for glioblastomaR01CA273319 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., SHONKA, NICOLE · 2022 to 2025
$2.2M
Novel Therapy to Inhibit IPMN ProgressionR01CA263575 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI BATRA, SURINDER K., MALAFA, MOKENGE P. · 2022 to 2024
$2.1M
Role of PD2/Paf1 in Pancreatic Acinar to Ductal MetaplasiaR01CA210637 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., PONNUSAMY, MOORTHY P. · 2017 to 2021
$2.0M
Targeting CXCR2 axis in Pancreatic CancerR01CA228524 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., SINGH, RAKESH K · 2018 to 2022
$2.0M
Rac1 GTPase in tumorigenesis and progression of pancreatic cancerR01CA206444 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., OUELLETTE, MICHEL M · 2016 to 2020
$1.9M
Genome-wide mechanisms and dynamics of ATP-dependent chromatin remodeling complexesR00GM138920 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BRAHMA, SANDIPAN · 2023 to 2025
$747k
NCI NIH HHS P01 CA217798NCI NIH HHS R01 CA206444NCI NIH HHS R01 CA210637NCI NIH HHS R01 CA228524NCI NIH HHS R01 CA256973NCI NIH HHS R01 CA263575NCI NIH HHS R01 CA273319NCI NIH HHS R01 CA273349NCI NIH HHS U01 CA200466NCI NIH HHS U01 CA210240NIGMS NIH HHS R00 GM138920
6 · The paper itself

Abstract

Pancreatic cancer (PC) is a highly aggressive malignancy, with cancer stem cells (CSCs) playing a critical role in metastasis, therapy resistance, and recurrence, thereby presenting significant treatment challenges. Emerging evidence suggests that normal embryonic and adult progenitor stem cells share common gene signatures with CSCs. However, the early pluripotency-associated factors and stemness programs that become aberrantly reactivated during oncogenic transformation remain poorly defined. Here, we identify SLC22A3/OCT3 (Solute Carrier Family 22 Member 3) as a reactivated embryonic-associated signature that regulates PC stemness. SLC22A3 is markedly upregulated in CSC-enriched populations, and its silencing in PC cells grown in both 2D cultures and 3D organoid models significantly reduces key stemness features. Moreover, serotonin (5-HT) transport, mediated by SLC22A3, enhances overall stemness via downstream histone modifications, linking serotonin signaling to CSC regulation. Collectively, these findings establish SLC22A3 as a regulator of serotonin-driven stemness and a potential therapeutic target in PC.

Indexed as

Neoplastic Stem CellsOrganic Cation Transporter 3Pancreatic NeoplasmsSerotoninAnimalsCell Line, TumorGene Expression Regulation, NeoplasticHistonesHumansSignal TransductionHistonesOrganic Cation Transporter 3SerotoninCP: cancerCP: stem cell researchhistone serotonylationpancreatic cancer stem cellsself-renewalserotonin signalingserotonin transporterSLC22A3/OCT3

Identifiers

PMID42250222
PMCPMC13638026

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