PMID- 30280201 OWN - NLM STAT- MEDLINE DCOM- 20190307 LR - 20190716 IS - 1791-2423 (Electronic) IS - 1019-6439 (Linking) VI - 53 IP - 6 DP - 2018 Dec TI - Metastatic cancer cells compensate for low energy supplies in hostile microenvironments with bioenergetic adaptation and metabolic reprogramming. PG - 2590-2604 LID - 10.3892/ijo.2018.4582 [doi] AB - Metastasis accounts for the majority of cancer-related mortalities, and the complex processes of metastasis remain the least understood aspect of cancer biology. Metabolic reprogramming is associated with cancer cell survival and metastasis in a hostile envi-ronment with a limited nutrient supply, such as solid tumors. Little is known regarding the differences of bioenergetic adaptation between primary tumor cells and metastatic tumor cells in unfavorable microenvironments; to clarify these differences, the present study aimed to compare metabolic reprogramming of primary tumor cells and metastatic tumor cells. SW620 metastatic tumor cells exhibited stronger bioenergetic adaptation in unfavorable conditions compared with SW480 primary tumor-derived cells, as determined by the sustained elevation of glycolysis and regulation of the cell cycle. This remarkable glycolytic ability of SW620 cells was associated with high expression levels of hexokinase (HK)1, HK2, glucose transporter type 1 and hypoxia-inducible factor 1alpha. Compared with SW480 cells, the expression of cell cycle regulatory proteins was effectively inhibited in SW620 cells to sustain cell survival when there was a lack of energy. Furthermore, SW620 cells exhibited a stronger mesenchymal phenotype and stem cell characteristics compared with SW480 cells; CD133 and CD166 were highly expressed in SW620 cells, whereas expression was not detected in SW480 cells. These data may explain why metastatic cancer cells exhibit greater microenvironmental adaptability and survivability; specifically, this may be achieved by upregulating glycolysis, optimizing the cell cycle and reprogramming cell metabolism. The present study may provide a target metabolic pathway for cancer metastasis therapy. FAU - Cheng, Yunlong AU - Cheng Y AD - Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou, Fujian 350116, P.R. China. FAU - Lu, Yusheng AU - Lu Y AD - Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou, Fujian 350116, P.R. China. FAU - Zhang, Doudou AU - Zhang D AD - Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou, Fujian 350116, P.R. China. FAU - Lian, Shu AU - Lian S AD - Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou, Fujian 350116, P.R. China. FAU - Liang, Haiyan AU - Liang H AD - Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou, Fujian 350116, P.R. China. FAU - Ye, Yuying AU - Ye Y AD - Fujian Provincial People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350004, P.R. China. FAU - Xie, Ruizhi AU - Xie R AD - Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou, Fujian 350116, P.R. China. FAU - Li, Shuhui AU - Li S AD - Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou, Fujian 350116, P.R. China. FAU - Chen, Jiahang AU - Chen J AD - Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou, Fujian 350116, P.R. China. FAU - Xue, Xuhui AU - Xue X AD - Xi'an Children Hospital, Xi'an, Shaanxi 710003, P.R. China. FAU - Xie, Jingjing AU - Xie J AD - Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou, Fujian 350116, P.R. China. FAU - Jia, Lee AU - Jia L AD - Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou, Fujian 350116, P.R. China. LA - eng PT - Comparative Study PT - Journal Article DEP - 20181002 PL - Greece TA - Int J Oncol JT - International journal of oncology JID - 9306042 RN - 0 (Glucose Transporter Type 1) RN - 0 (HIF1A protein, human) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (SLC2A1 protein, human) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - EC 2.7.1.1 (HK1 protein, human) RN - EC 2.7.1.1 (HK2 protein, human) RN - EC 2.7.1.1 (Hexokinase) SB - IM MH - Adenosine Triphosphate/*metabolism MH - Animals MH - Cell Cycle MH - Cell Line, Tumor MH - Cell Survival MH - Colonic Neoplasms/genetics/metabolism/*pathology MH - Energy Metabolism MH - Gene Expression Regulation, Neoplastic MH - Glucose Transporter Type 1/genetics/metabolism MH - *Glycolysis MH - Hexokinase/genetics/metabolism MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism MH - Membrane Potential, Mitochondrial MH - Mice MH - Neoplasm Metastasis MH - Neoplasm Transplantation MH - Neoplastic Stem Cells/*metabolism EDAT- 2018/10/04 06:00 MHDA- 2019/03/08 06:00 CRDT- 2018/10/04 06:00 PHST- 2018/01/10 00:00 [received] PHST- 2018/06/18 00:00 [accepted] PHST- 2018/10/04 06:00 [pubmed] PHST- 2019/03/08 06:00 [medline] PHST- 2018/10/04 06:00 [entrez] AID - 10.3892/ijo.2018.4582 [doi] PST - ppublish SO - Int J Oncol. 2018 Dec;53(6):2590-2604. doi: 10.3892/ijo.2018.4582. Epub 2018 Oct 2.