2. Academic Validation
  3. The mevalonate coordinates energy input and cell proliferation

The mevalonate coordinates energy input and cell proliferation

  • Cell Death Dis. 2019 Apr 11;10(4):327. doi: 10.1038/s41419-019-1544-y.
Li Gong 1,  Yi Xiao 1,  Fan Xia 1 2 3,  Pei Wu 1,  Tingting Zhao 1,  Shulin Xie 4,  Ran Wang 5,  Qiaocheng Wen 5,  Wensu Zhou 6,  Huilan Xu 6,  Lingyan Zhu 1 7,  Zeqi Zheng 2 3,  Tianlun Yang 1,  Zihua Chen 8,  Qiong Duan 9 10
Affiliations

Affiliations

  • 1 Department of Cardiology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, China.
  • 2 Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
  • 3 Jiangxi Hypertension Research Institute, Nanchang, China.
  • 4 Department of Anesthesiology, Taojiang People's Hospital, Taojiang, Hunan, China.
  • 5 Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China.
  • 6 Department of Social Medicine and Health Administration, Xiangya School of Public Health, Central South University, Changsha, China.
  • 7 Department of Endocrinology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
  • 8 Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China. zihuac@outlook.com.
  • 9 Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang, China. qiongduan@csu.edu.cn.
  • 10 Jiangxi Hypertension Research Institute, Nanchang, China. qiongduan@csu.edu.cn.
PMID: 30975976 DOI: 10.1038/s41419-019-1544-y
Abstract

The mevalonate pathway is known for the synthesis of Cholesterol, but recent studies have reported that it also controls Hippo signaling, which is critical for the regulation of organ size and tumorigenesis. Here, we discover that the suppression of the mevalonate pathway inhibits the growth and proliferation of colon Cancer cell lines. The results of transcriptomic and proteomic assays suggested that the mevalonate pathway controls multiple signaling pathways relevant to cell proliferation, and the results were further confirmed using western blot, PCR, and immunofluorescence assays. As cell proliferation is an energy-consuming process, we postulate that the mevalonate pathway may also control nutrient uptake to coordinate the processes of energy supply and cell proliferation. Here, we found that lovastatin, a mevalonate pathway inhibitor, suppresses glucose and amino acid uptake and lactate acid production. More importantly, mevalonic acid itself is sufficient to promote glucose uptake by colon Cancer cells. In addition, we found that colon Cancer tissues displayed a higher expression of mevalonate pathway Enzymes, which may promote cell growth and stimulate energy uptake. Together, our findings establish the mevalonate pathway as a critical regulator in coordinating energy input and cell proliferation.

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