Mazziotta C, Rotondo JC. Unraveling the role of flotillin-1 in driving hepatocellular carcinoma progression through transcription factor E3-mediated Golgi stress response. World J Gastroenterol 2025; 31(38): 112489 [DOI: 10.3748/wjg.v31.i38.112489]
Corresponding Author of This Article
Chiara Mazziotta, PhD, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, United States. chiara_mazziotta@dfci.harvard.edu
Research Domain of This Article
Oncology
Article-Type of This Article
Editorial
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
World J Gastroenterol. Oct 14, 2025; 31(38): 112489 Published online Oct 14, 2025. doi: 10.3748/wjg.v31.i38.112489
Unraveling the role of flotillin-1 in driving hepatocellular carcinoma progression through transcription factor E3-mediated Golgi stress response
Chiara Mazziotta, John Charles Rotondo
Chiara Mazziotta, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, United States
John Charles Rotondo, IRCCS Ospedale Policlinico San Martino, Genoa 16132, Liguria, Italy
Co-corresponding authors: Chiara Mazziotta and John Charles Rotondo.
Author contributions: Rotondo JC and Mazziotta C contributed to the writing and editing, review of literature, and made equal contributions as co-corresponding authors; Rotondo JC designed the overall concept and outline of the manuscript; Mazziotta C contributed to the discussion and design of the manuscript. Both of authors approved the final version to publish.
Supported by Italian Association for Cancer Research (AIRC), No. 21956; Italian Ministry of Health - 5 × 1000 funds 2023.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest 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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Chiara Mazziotta, PhD, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, United States. chiara_mazziotta@dfci.harvard.edu
Received: July 28, 2025 Revised: August 12, 2025 Accepted: September 16, 2025 Published online: October 14, 2025 Processing time: 77 Days and 20 Hours
Core Tip
Core Tip: Hepatocellular carcinoma (HCC) is currently considered a primary contributor of cancer-associated mortality on a global scale. The authors elucidate a novel mechanism whereby the lipid raft protein flotillin-1 (FLOT1) drives HCC progression through transcription factor E3-mediated Golgi stress response. FLOT1 overexpression enhanced proliferation, migration and invasion, and suppressed apoptosis in vitro and in mice, whereas gene silencing reversed these phenotypes. Mechanistically, FLOT1 inhibits mechanistic target of rapamycin complexes 1 and 2 via ubiquitination, promoting transcription factor E3 dephosphorylation and subsequent nuclear translocation, resulting in enhanced expression of multiple genes involved in Golgi stress response. These findings advance our understanding of lipid raft-associated proteins in cancer and propose FLOT1 as a potential target for the treatment of HCC.
