SLC22A3/OCT3 Drives Serotonin-Mediated Stemness in Pancreatic Cancer

Authors

• Nivedeta Krishna Kumar, University of Nebraska Medical Center
• Venkatesh Varadharaj, University of Nebraska Medical CenterFollow
• Neelanjana Gayen, University of Nebraska Medical CenterFollow
• Annant Bir Kaur, University of Nebraska Medical CenterFollow
• Kirtana Arikath, University of Nebraska Medical CenterFollow
• Ashu Shah, University of Nebraska Medical CenterFollow
• Poompozhil Mathivanan, University of Nebraska Medical CenterFollow
• Palanisamy Nallasamy, University of Nebraska Medical CenterFollow
• Zahraa Wajih Alsafwani, University of Nebraska Medical CenterFollow
• Bhuvaneshwari Seshadri, University of Nebraska Medical Center
• Pratima Raut, University of Nebraska Medical Center
• Sanchita Rauth, University of Nebraska Medical CenterFollow
• Jimmie Persinger, University of Nebraska Medical CenterFollow
• Sandipan Brahma, University of Nebraska Medical CenterFollow
• Micah Schott, University of Nebraska Medical CenterFollow
• Rebecca E. Oberley-Deegan, University of Nebraska Medical CenterFollow
• Geoffrey A. Talmon, University of Nebraska Medical CenterFollow
• Jesse L. Cox, University of Nebraska Medical CenterFollow
• Surinder K. Batra, University of Nebraska Medical CenterFollow
• Moorthy P. Ponnusamy, University of Nebraska Medical CenterFollow

Document Type

Article

Journal Title

Cell Reports

Publication Date

2026

Volume

45

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.

ISSN

2211-1247

DOI Link

10.1016/j.celrep.2026.117387

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Recommended Citation

Krishna Kumar, Nivedeta; Varadharaj, Venkatesh; Gayen, Neelanjana; Kaur, Annant Bir; Arikath, Kirtana; Shah, Ashu; Mathivanan, Poompozhil; Nallasamy, Palanisamy; Alsafwani, Zahraa Wajih; Seshadri, Bhuvaneshwari; Raut, Pratima; Rauth, Sanchita; Persinger, Jimmie; Brahma, Sandipan; Schott, Micah; Oberley-Deegan, Rebecca E.; Talmon, Geoffrey A.; Cox, Jesse L.; Batra, Surinder K.; and Ponnusamy, Moorthy P., "SLC22A3/OCT3 Drives Serotonin-Mediated Stemness in Pancreatic Cancer" (2026). Journal Articles: Biochemistry & Molecular Biology. 185.
https://digitalcommons.unmc.edu/com_bio_articles/185