Publication Name	World Journal of Gastroenterology
Manuscript ID	112489
Country	United States

Category	Oncology
Manuscript Type	Editorial
Article Title	Unraveling the role of flotillin-1 in driving hepatocellular carcinoma progression through transcription factor E3-mediated Golgi stress response
Manuscript Source	Invited Manuscript
All Author List	Chiara Mazziotta and John Charles Rotondo
Funding Agency and Grant Number	Funding Agency Grant Number Italian Association for Cancer Research (AIRC) 21956 Italian Ministry of Health - 5 × 1000 funds 2023
Corresponding Author	Chiara Mazziotta, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, United States. chiara_mazziotta@dfci.harvard.edu
Key Words	Hepatocellular carcinoma; Transcription factor E3; Flotillin-1; Mechanistic target of rapamycin complexes 1 and 2; Golgi stress
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, 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.
Citation	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; In press

Received	2025-07-28 14:23
Peer-Review Started	2025-07-28 14:23
To Make the First Decision
Return for Revision	2025-08-01 10:09
Revised	2025-08-12 19:23
Second Decision	2025-09-16 02:35
Accepted by Journal Editor-in-Chief
Accepted by Executive Editor-in-Chief	2025-09-16 03:11
Articles in Press	2025-09-16 03:11
Publication Fee Transferred
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	1007-9327 (print) and 2219-2840 (online)
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