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journal article·2026-04Open access

Cancer Cell‐Intrinsic Cholesterol Induces Lipid‐Associated Macrophage Differentiation via SP1 Palmitoylation to Promote Prostate Cancer Progression

Shirong Peng, Weilong Lin, Zean Li, Ruilin Zhuang, Shengmeng Peng, Bingheng Li, Bingliang Chen, Yong Luo, Yuan Ou, Wei Zhuang, Tao Du, Kaiwen Li, Hai Huang

Advanced Science· Volume 13· Issue 19
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Source abstract

Abstract

ABSTRACT Cholesterol metabolism influences prostate cancer (PCa) progression, especially by affecting the tumor microenvironment. The present study demonstrated that cancer cell‐intrinsic cholesterol promoted the S‐palmitoylation of specificity protein 1 (SP1), enhancing SP1 nuclear translocation and driving the transcription and secretion of midkine (MDK), which in turn facilitated the differentiation of macrophages into a lipid‐associated phenotype. Furthermore, targeting cholesterol metabolism with simvastatin significantly reduced MDK levels, inhibited immunosuppressive macrophage polarization, and enhanced the efficacy of enzalutamide in vivo. These findings suggested that targeting the cancer cell‐intrinsic cholesterol‐induced immunosuppressive tumor microenvironment could be an effective strategy to improve therapeutic outcomes in prostate cancer patients.
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Research context

OpenAlex topics: Cancer, Lipids, and Metabolism · Immune cells in cancer · Cancer Research and Treatments

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Urology Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Guangzhou China

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong‐Hong Kong Joint Laboratory for RNA Medicine Urology Department Sun Yat‐Sen Memorial Hospital Sun Yat‐Sen University Guangzhou China

Department of Urology The Second Affiliated Hospital of Fujian Medical University Quanzhou Fujian China

Department of Obstetrics and Gynecology Sun Yat‐Sen Memorial Hospital Sun Yat‐Sen University Guangzhou Guangdong China

Guangdong Provincial Clinical Research Center for Urological Diseases Sun Yat‐Sen Memorial Hospital Sun Yat‐Sen University Guangzhou China

Department of Urology The Sixth Affiliated Hospital of Guangzhou Medical University Qingyuan People's Hospital Qingyuan Guangdong China

Funding

National Natural Science Foundation of China · Beijing Xisike Clinical Oncology Research Foundation · Natural Science Foundation of Guangdong Province

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