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World J Gastroenterol. Oct 14, 2021; 27(38): 6387-6398
Published online Oct 14, 2021. doi: 10.3748/wjg.v27.i38.6387
Transcription factors specificity protein and nuclear receptor 4A1 in pancreatic cancer
Stephen Safe, Rupesh Shrestha, Kumaravel Mohankumar, Marcell Howard, Erik Hedrick, Maen Abdelrahim
Stephen Safe, Kumaravel Mohankumar, Marcell Howard, Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77845, United States
Rupesh Shrestha, Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77845, United States
Erik Hedrick, Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, United States
Maen Abdelrahim, Department of Medical Oncology, Houston Methodist Hospital Cancer Center, Houston, TX 77030, United States
Author contributions: Safe S, Abdelrahim M and Hedrick E substantial contributions to conception and design of the study, acquisition of data, or analysis and interpretation of data; Shrestha R and Howard M drafting the article or making critical revisions related to important intellectual content of the manuscript; Safe S, Mohankumar K and Shrestha R final approval of the version of the article to be published.
Supported by Houston Methodist Cancer Center Innovation Award.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Stephen Safe, PhD, Full Professor, Department of Veterinary Physiology and Pharmacology, Texas A&M University, 4466 TAMU, College Station, TX 77845, United States. ssafe@cvm.tamu.edu
Received: January 14, 2021
Peer-review started: January 14, 2021
First decision: March 29, 2021
Revised: April 30, 2021
Accepted: September 6, 2021
Article in press: September 6, 2021
Published online: October 14, 2021
Core Tip

Core Tip: Specificity protein (Sp), transcription factors (TFs), Sp1, Sp3 and Sp4, and nuclear receptor 4A1 (NR4A1, Nur77) are highly expressed in pancreatic cancer cells and tumors. Results of gene silencing studies show that Sp TFs and NR4A1 are pro-oncogenic and regulate pathways/genes associated with cell proliferation, survival and migration/invasion. Bis-indole derived ligands (CDIMs) that bind NR4A1 act as NR4A1 antagonists and we discuss an important mechanism of gene regulation by NR4A1/Sp complexes which can be inhibited by NR4A1 antagonists.