Rajan Radha Rasmi and Kunnathur Murugesan Sakthivel (2025) Targeting SREBP2 in cancer progression: Molecular mechanisms, oncogenic crosstalk, and therapeutic interventions. Targeting SREBP2 in cancer progression: Molecular mechanisms, oncogenic crosstalk, and therapeutic interventions, 135. pp. 1-14. ISSN 0898-6568

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Abstract

Cholesterol, an essential membrane component and a precursor for steroid hormones and bile acids, plays a vital
role in various cellular processes. Cancer cells, in particular, exhibit a heightened demand for cholesterol to
support their proliferation. This increased cholesterol requirement can be attributed to the upregulation of
cholesterol biosynthesis or enhanced cholesterol uptake. Metabolic reprogramming in cancer cells allows them to
sustain the energy demands associated with their aberrant growth characteristics. In normal cells, cholesterol
uptake and synthesis are tightly regulated through various mechanisms within the cholesterol metabolism
pathway. SREBP2 (Sterol Regulatory Element Binding Protein 2) is a critical master regulator of cholesterol
homeostasis in normal cells. Dysregulation of cholesterol metabolism is intricately linked with the development
of malignant phenotypes. Furthermore, emerging evidence highlights the crosstalk between SREBP2 and aber
rant signaling pathways, such as PI3K/AKT/mTORC1, p53, TGF-β, c-Myc, Hippo, and FoxM1, which promote
tumorigenesis. Understanding these molecular interactions between SREBP2 and signaling pathways is crucial
for unraveling the mechanisms underlying cancer development. Identifying combinatorial treatment strategies
targeting cholesterol metabolism holds great promise in deciphering mechanistic insights into metabolic vul
nerabilities in cancer cells. Such strategies have the potential to enhance the efficacy of standard chemo/
radiotherapy approaches for highly resistant cancer types. This review explores the regulation of SREBP2 in
cancer and elucidates its role in dysregulated cholesterol metabolism. A detailed discussion on the implications of
targeting cholesterol metabolism as a therapeutic approach for cancer treatment has also been elucidated

Item Type: Article
Additional Information: journal homepage: www.elsevier.com/locate/cellsig
Uncontrolled Keywords: Cholesterol Sterol regulatory element binding protein 2 (SREBP2) Cancer Combinatorial targeted therapeutics
Divisions: PSG College of Arts and Science > Department of Biochemistry
Depositing User: Dr. B Sivakumar
Date Deposited: 02 Dec 2025 12:19
Last Modified: 03 Dec 2025 05:39
URI: https://ir.psgcas.ac.in/id/eprint/2550

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