NYMC Faculty Publications
Inhibition of NAMPT as a Therapeutic Strategy to Suppress Tumor Growth in Lymphangioleiomyomatosis
Author Type(s)
Student, Faculty
DOI
10.1016/j.bbamcr.2025.119986
Journal Title
Biochimica Et Biophysica Acta Molecular Cell Research
Document Type
Article
Publication Date
8-1-2025
Department
Cell Biology and Anatomy
Keywords
AMP-activated protein kinase (AMPK), Autophagy, FK866, Lymphangioleiomyomatosis (LAM), Mechanistic target of rapamycin (mTOR), Nicotinamide Phosphoribosyltransferase (NAMPT), Targeted therapy, Tuberous sclerosis complex (TSC)
Disciplines
Medicine and Health Sciences
Abstract
Lymphangioleiomyomatosis (LAM) is a rare, progressive lung disease driven by mutations in the TSC1 or TSC2 genes, leading to constitutive mTORC1 activation and uncontrolled cell proliferation. Current therapies, like rapamycin effectively stabilize disease progression but mainly exert cytostatic effects and promote autophagy, a survival mechanism in LAM cells. These limitations highlight the need for the development of innovative therapies to achieve more effective and lasting results. To explore alternative therapeutic targets, we investigated the role of nicotinamide phosphoribosyltransferase (NAMPT), a key regulator of NAD+ biosynthesis, in LAM and TSC2-deficient cells using a potent inhibitor, FK866. Our study demonstrates that FK866 depletes NAD+ levels in these cells, exerting a dual effect by activating AMPK and subsequently inhibiting mTORC1 signaling while suppressing autophagy. Unlike rapamycin, FK866 does not induce compensatory Akt activation, significantly inhibits LAM cell proliferation and induces apoptosis. Additionally, using an in vivo chicken egg chorioallantoic membrane (CAM) model, we showed that FK866 treatment significantly reduces LAM tumor growth compared to controls suggesting that NAMPT inhibition disrupts metabolic and survival pathways critical for TSC2-deficient cell viability and tumor progression. Our results establish NAMPT as a promising therapeutic target for LAM, offering a two-prong strategy to suppress tumor growth and enhance apoptosis, providing an alternative to current mTOR-based therapies.
Recommended Citation
Fard, S., Kundu, N., Torres, A., Faltas, C., Di Martino, J., & Holz, M. (2025). Inhibition of NAMPT as a Therapeutic Strategy to Suppress Tumor Growth in Lymphangioleiomyomatosis. Biochimica Et Biophysica Acta Molecular Cell Research, 1872 (6). https://doi.org/10.1016/j.bbamcr.2025.119986
