The mevalonate coordinates energy input and cell proliferation
| Autor: | Tianlun Yang, Zihua Chen, Ran Wang, Qiong Duan, Li Gong, Fan Xia, Wensu Zhou, Zeqi Zheng, Qiaocheng Wen, Pei Wu, Shulin Xie, Huilan Xu, Lingyan Zhu, Yi Xiao, Tingting Zhao |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Proteomics
0301 basic medicine Cancer Research Immunology Mevalonic Acid Mevalonic acid medicine.disease_cause Article 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor medicine Humans Lovastatin lcsh:QH573-671 Amino Acids Wnt Signaling Pathway Adaptor Proteins Signal Transducing Cell Proliferation lcsh:Cytology Cholesterol Cell growth YAP-Signaling Proteins Cell Biology Cell biology Glucose 030104 developmental biology chemistry Cell culture Hippo signaling 030220 oncology & carcinogenesis Colonic Neoplasms Mevalonate pathway Signal transduction Carcinogenesis Signal Transduction Transcription Factors |
| Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 10, Iss 4, Pp 1-14 (2019) |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-019-1544-y |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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