2. Academic Validation
  3. Tumor Cell "Slimming" Regulates Tumor Progression through PLCL1/UCP1-Mediated Lipid Browning

Tumor Cell "Slimming" Regulates Tumor Progression through PLCL1/UCP1-Mediated Lipid Browning

  • Adv Sci (Weinh). 2019 Mar 25;6(10):1801862. doi: 10.1002/advs.201801862.
Zhiyong Xiong 1 2,  Wen Xiao 1 2,  Lin Bao 1 2,  Wei Xiong 1 2,  Haibing Xiao 1 2,  Yan Qu 3,  Changfei Yuan 1 2,  Hailong Ruan 1 2,  Qi Cao 1 2,  Keshan Wang 1 2,  Zhengshuai Song 1 2,  Cheng Wang 1 2,  Wenjun Hu 3,  Zeyuan Ru 3,  Junwei Tong 1 2,  Gong Cheng 1 2,  Tianbo Xu 1 2,  Xiangui Meng 1 2,  Jian Shi 1 2,  Zhixian Chen 1 2,  Hongmei Yang 3,  Ke Chen 1 2,  Xiaoping Zhang 1 2
Affiliations

Affiliations

  • 1 Department of Urology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China.
  • 2 Institute of Urology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China.
  • 3 Department of Pathogenic Biology School of Basic Medicine Huazhong University of Science and Technology Wuhan 430030 China.
PMID: 31131187 DOI: 10.1002/advs.201801862
Abstract

Emerging evidence has highlighted the important role of abnormal lipid accumulation in Cancer development and progression, but the mechanism for this phenomenon remains unclear. Here, it is demonstrated that Phospholipase C-like 1/uncoupling protein 1 (PLCL1)/(UCP1)-mediated lipid browning promotes tumor cell "slimming" and represses tumor progression. By screening three independent lipid metabolism-related gene sets in clear cell renal cell carcinoma (ccRCC) and analyzing the TCGA database, it is found that PLCL1 predicted a poor prognosis and was downregulated in ccRCC. Restoration of PLCL1 expression in ccRCC cells significantly represses tumor progression and reduces abnormal lipid accumulation. Additionally, a phenomenon called tumor cell "slimming," in which tumor cell volume is reduced and lipid droplets are transformed into tiny pieces, is observed. Further studies show that PLCL1 promotes tumor cell "slimming" and represses tumor progression through UCP1-mediated lipid browning, which consumes lipids without producing ATP energy. Mechanistic investigations demonstrate that PLCL1 improves the protein stability of UCP1 by influencing the level of protein ubiquitination. Collectively, the data indicate that lipid browning mediated by PLCL1/UCP1 promotes tumor cell "slimming" and consumes abnormal lipid accumulation, which represses the progression of ccRCC. Tumor cell "slimming" offers a promising new concept and treatment modality against tumor development and progression.

Keywords

PLCL1; UCP1; clear cell renal cell carcinoma; lipid browning; tumor cell “slimming”.

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