The role of 7-dehydrocholesterol in inducing ER stress and apoptosis of head and neck squamous cell carcinoma

Authors
Lee, Bok-SoonPark, Yea-InLiu, HengtianKim, Sang GyuKim, Hyo JeongChoi, Ji-HyeRho, Si HyunPadilla, JoselynRoh, JinWoo, Hyun GooSeo, Hae JinChoi, Man HoJeong, Yu-JinLien, Evan C.Mehdi, Syed HassanLee, DongjoonYoon, DonghoonKim, Chul-HoLee, Jiyoung
Issue Date
2025-09
Publisher
Elsevier BV
Citation
Cancer Letters, v.628
Abstract
Alterations of metabolic pathways that sustain cancer cell survival often offer promising therapeutic avenues. Here, we show that enhanced de novo cholesterol biosynthesis is crucial for the survival of head and neck squamous cell carcinoma (HNSCC). Transcriptomic analysis of HNSCC tissues identified profound dysregulation in steroid and cholesterol metabolism compared to normal tissues. Inhibition of two key enzymes, DHCR7 and DHCR24, which mediate cholesterol biosynthesis, induced apoptosis in HNSCC cells, even when cholesterol levels were restored. Metabolomic profiling revealed the accumulation of 7-dehydrocholesterol (7-DHC) upon DHCR7 or DHCR24 inhibition, triggering endoplasmic reticulum (ER) stress and promoting further cell death. These findings suggest that HNSCC cells adapt to ER stress by modulating 7-DHC levels through enhancing DHCR7 and DHCR24 levels, highlighting a metabolic vulnerability in HNSCC and demonstrating a direct link between cholesterol metabolism and ER stress in cancer cell viability.
Keywords
CHOLESTEROL-METABOLISM; CANCER; OXYSTEROLS; RISK; MS; Cholesterol metabolism; DHCR7; DHCR24; 7-Dehydrocholesterol; Head and neck cancer; ER stress
ISSN
0304-3835
URI
https://pubs.kist.re.kr/handle/201004/152692
DOI
10.1016/j.canlet.2025.217842
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KIST Article > Others
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