Advances in regulation and function of stearoyl-CoA desaturase 1 in cancer, from bench to bed

doi:10.1007/s11427-023-2352-9

Review

. 2023 Dec;66(12):2773-2785.

doi: 10.1007/s11427-023-2352-9. Epub 2023 Jul 11.

Advances in regulation and function of stearoyl-CoA desaturase 1 in cancer, from bench to bed

Zhengyang Guo^#¹, Xiao Huo^#¹, Xianlong Li¹, Changtao Jiang^{2

3}, Lixiang Xue^{4

5}

Affiliations

¹ Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, 100191, China.
² Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, 100191, China. jiangchangtao@bjmu.edu.cn.
³ Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University and the Key Laboratory of Molecular Cardiovascular Science (Peking University), Ministry of Education, Beijing, 100191, China. jiangchangtao@bjmu.edu.cn.
⁴ Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, 100191, China. lixiangxue@hsc.pku.edu.cn.
⁵ Peking University Third Hospital Cancer Center, Department of Radiation Oncology, Peking University Third Hospital, Beijing, 100191, China. lixiangxue@hsc.pku.edu.cn.

^# Contributed equally.

PMID: 37450239
DOI: 10.1007/s11427-023-2352-9

Review

Advances in regulation and function of stearoyl-CoA desaturase 1 in cancer, from bench to bed

Zhengyang Guo et al. Sci China Life Sci. 2023 Dec.

. 2023 Dec;66(12):2773-2785.

doi: 10.1007/s11427-023-2352-9. Epub 2023 Jul 11.

Authors

Zhengyang Guo^#¹, Xiao Huo^#¹, Xianlong Li¹, Changtao Jiang^{2

3}, Lixiang Xue^{4

5}

Affiliations

¹ Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, 100191, China.
² Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, 100191, China. jiangchangtao@bjmu.edu.cn.
³ Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University and the Key Laboratory of Molecular Cardiovascular Science (Peking University), Ministry of Education, Beijing, 100191, China. jiangchangtao@bjmu.edu.cn.
⁴ Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, 100191, China. lixiangxue@hsc.pku.edu.cn.
⁵ Peking University Third Hospital Cancer Center, Department of Radiation Oncology, Peking University Third Hospital, Beijing, 100191, China. lixiangxue@hsc.pku.edu.cn.

^# Contributed equally.

PMID: 37450239
DOI: 10.1007/s11427-023-2352-9

Abstract

Stearoyl-CoA desaturase 1 (SCD1) converts saturated fatty acids to monounsaturated fatty acids. The expression of SCD1 is increased in many cancers, and the altered expression contributes to the proliferation, invasion, sternness and chemoresistance of cancer cells. Recently, more evidence has been reported to further support the important role of SCD1 in cancer, and the regulation mechanism of SCD1 has also been focused. Multiple factors are involved in the regulation of SCD1, including metabolism, diet, tumor microenvironment, transcription factors, non-coding RNAs, and epigenetics modification. Moreover, SCD1 is found to be involved in regulating ferroptosis resistance. Based on these findings, SCD1 has been considered as a potential target for cancer treatment. However, the resistance of SCD1 inhibition may occur in certain tumors due to tumor heterogeneity and metabolic plasticity. This review summarizes recent advances in the regulation and function of SCD1 in tumors and discusses the potential clinical application of targeting SCD1 for cancer treatment.

Keywords: ER stress; SCD1; cancer metabolism; cancer therapy; drug resistance; fatty acid; ferroptosis; lipid metabolism.

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References

1. Ackerman, D., and Simon, M.C. (2014). Hypoxia, lipids, and cancer: surviving the harsh tumor microenvironment. Trends Cell Biol 24, 472–478. - PubMed - PMC
1. Ackerman, D., Tumanov, S., Qiu, B., Michalopoulou, E., Spata, M., Azzam, A., Xie, H., Simon, M.C., and Kamphorst, J.J. (2018). Triglycerides promote lipid homeostasis during hypoxic stress by balancing fatty acid saturation. Cell Rep 24, 2596–2605.e5. - PubMed - PMC
1. ALJohani, A.M., Syed, D.N., and Ntambi, J.M. (2017). Insights into stearoyl-CoA desaturase-1 regulation of systemic metabolism. Trends Endocrinol Metab 28, 831–842. - PubMed - PMC
1. Ascenzi, F., De Vitis, C., Maugeri-Saccà, M., Napoli, C., Ciliberto, G., and Mancini, R. (2021). SCD1, autophagy and cancer: implications for therapy. J Exp Clin Cancer Res 40, 265. - PubMed - PMC
1. Badur, M.G., Muthusamy, T., Parker, S.J., Ma, S., McBrayer, S.K., Cordes, T., Magana, J.H., Guan, K.L., and Metallo, C.M. (2018). Oncogenic R132 IDH1 mutations limit NADPH for de novo lipogenesis through (D)2-hydroxyglutarate production in fibrosarcoma cells. Cell Rep 25, 1018–1026.e4. - PubMed - PMC

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[1] Ackerman, D., and Simon, M.C. (2014). Hypoxia, lipids, and cancer: surviving the harsh tumor microenvironment. Trends Cell Biol 24, 472–478. - PubMed - PMC

[2] Ackerman, D., and Simon, M.C. (2014). Hypoxia, lipids, and cancer: surviving the harsh tumor microenvironment. Trends Cell Biol 24, 472–478. - PubMed - PMC

[3] Ackerman, D., Tumanov, S., Qiu, B., Michalopoulou, E., Spata, M., Azzam, A., Xie, H., Simon, M.C., and Kamphorst, J.J. (2018). Triglycerides promote lipid homeostasis during hypoxic stress by balancing fatty acid saturation. Cell Rep 24, 2596–2605.e5. - PubMed - PMC

[4] Ackerman, D., Tumanov, S., Qiu, B., Michalopoulou, E., Spata, M., Azzam, A., Xie, H., Simon, M.C., and Kamphorst, J.J. (2018). Triglycerides promote lipid homeostasis during hypoxic stress by balancing fatty acid saturation. Cell Rep 24, 2596–2605.e5. - PubMed - PMC

[5] ALJohani, A.M., Syed, D.N., and Ntambi, J.M. (2017). Insights into stearoyl-CoA desaturase-1 regulation of systemic metabolism. Trends Endocrinol Metab 28, 831–842. - PubMed - PMC

[6] ALJohani, A.M., Syed, D.N., and Ntambi, J.M. (2017). Insights into stearoyl-CoA desaturase-1 regulation of systemic metabolism. Trends Endocrinol Metab 28, 831–842. - PubMed - PMC

[7] Ascenzi, F., De Vitis, C., Maugeri-Saccà, M., Napoli, C., Ciliberto, G., and Mancini, R. (2021). SCD1, autophagy and cancer: implications for therapy. J Exp Clin Cancer Res 40, 265. - PubMed - PMC

[8] Ascenzi, F., De Vitis, C., Maugeri-Saccà, M., Napoli, C., Ciliberto, G., and Mancini, R. (2021). SCD1, autophagy and cancer: implications for therapy. J Exp Clin Cancer Res 40, 265. - PubMed - PMC

[9] Badur, M.G., Muthusamy, T., Parker, S.J., Ma, S., McBrayer, S.K., Cordes, T., Magana, J.H., Guan, K.L., and Metallo, C.M. (2018). Oncogenic R132 IDH1 mutations limit NADPH for de novo lipogenesis through (D)2-hydroxyglutarate production in fibrosarcoma cells. Cell Rep 25, 1018–1026.e4. - PubMed - PMC

[10] Badur, M.G., Muthusamy, T., Parker, S.J., Ma, S., McBrayer, S.K., Cordes, T., Magana, J.H., Guan, K.L., and Metallo, C.M. (2018). Oncogenic R132 IDH1 mutations limit NADPH for de novo lipogenesis through (D)2-hydroxyglutarate production in fibrosarcoma cells. Cell Rep 25, 1018–1026.e4. - PubMed - PMC

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Advances in regulation and function of stearoyl-CoA desaturase 1 in cancer, from bench to bed

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Advances in regulation and function of stearoyl-CoA desaturase 1 in cancer, from bench to bed

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