Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Sep 28:628:217842.
doi: 10.1016/j.canlet.2025.217842. Epub 2025 May 31.

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

Bok-Soon Lee  1 , Yea-In Park  2 , Hengtian Liu  2 , Sang Gyu Kim  3 , Hyo Jeong Kim  4 , Ji-Hye Choi  5 , Si Hyun Rho  3 , Joselyn Padilla  2 , Jin Roh  6 , Hyun Goo Woo  5 , Hae Jin Seo  7 , Man Ho Choi  7 , Yu-Jin Jeong  8 , Evan C Lien  8 , Syed Hassan Mehdi  9 , Dongjoon Lee  9 , Donghoon Yoon  9 , Chul-Ho Kim  10 , Jiyoung Lee  11
Affiliations

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

Bok-Soon Lee et al. Cancer Lett. .

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: 7-Dehydrocholesterol; Cholesterol metabolism; DHCR24; DHCR7; ER stress; Head and neck cancer.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

References

    1. Chow LQM Head and Neck Cancer. New England Journal of Medicine 382, 60–72 (2020). - PubMed
    1. Johnson DE et al. Head and neck squamous cell carcinoma. Nat Rev Dis Primers 6, 1–22 (2020). - PMC - PubMed
    1. Fakhry C. et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst 100, 261–269 (2008). - PubMed
    1. Vokes EE, Agrawal N. & Seiwert TY HPV-Associated Head and Neck Cancer. J Natl Cancer Inst 107, djv344 (2015). - PubMed
    1. Arteaga C. Targeting HER1/EGFR: a molecular approach to cancer therapy. Semin Oncol 30, 3–14 (2003). - PubMed

MeSH terms