Insulin Signalling-Inducible IFITM1 Promotes Multiple Myeloma Progression and Bortezomib Resistance
Ji-Young Lim1, Yeojin Kim1, Sung-Soo Park1
1Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
Journal of Cellular and Molecular Medicine
|June 13, 2026
Summary
Insulin excess fuels multiple myeloma (MM) growth by increasing Interferon-induced transmembrane protein 1 (IFITM1) expression, impacting patient prognosis and treatment resistance. IFITM1 is a potential therapeutic target in MM.
Area of Science:
- Oncology
- Molecular Biology
- Endocrinology
Background:
- Insulin promotes malignant cell growth, particularly in cancers overexpressing the insulin receptor (INSR).
- Insulin excess is a recognized cancer-promoting factor.
- Interferon-induced transmembrane protein 1 (IFITM1) is overexpressed in various cancers.
Purpose of the Study:
- To investigate the association between insulin signaling-induced IFITM1 expression and multiple myeloma (MM) aggressiveness.
- To determine IFITM1's role in MM cell proliferation, apoptosis, and response to proteasome inhibitors (PIs).
Main Methods:
- Quantified INSR and IFITM1 expression in MM patients.
- Correlated IFITM1 expression with prognosis and treatment outcomes.
- Assessed the impact of insulin, IGF-II, and IFITM1 on MM cell proliferation, apoptosis, and migration.
- Investigated IFITM1's role in bortezomib resistance.
Main Results:
- Both INSR and IFITM1 were significantly elevated in symptomatic MM patients.
- IFITM1 expression, not INSR, correlated with prognosis post-transplantation and bortezomib therapy.
- Insulin and IGF-II enhanced MM cell proliferation via IFITM1 upregulation.
- Insulin and IGF-II attenuated apoptosis and PIs' effects, which was reversed by IFITM1 knockdown.
- Insulin's reduction of bortezomib-induced apoptosis and cell cycle arrest was IFITM1-dependent.
Conclusions:
- Insulin-induced IFITM1 plays a critical role in MM progression and bortezomib resistance.
- IFITM1 is a potential prognostic biomarker for MM.
- IFITM1 represents a promising therapeutic target for multiple myeloma.
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