Upregulation of SCD1 by ErbB2 via LDHA promotes breast cancer cell migration and invasion

Med Oncol. 2022 Dec 5;40(1):40. doi: 10.1007/s12032-022-01904-8.

Abstract

The incidence of breast cancer ranks at the top of female malignant tumors in China. Metastasis remains the main cause of death among breast cancer patients. The overexpression of ErbB2 is closely related to the metastasis and poor prognosis of breast cancer patients. Therefore, ErbB2 is an important clinical therapeutic target of breast cancer. However, the molecular mechanism of ErbB2 promoting breast cancer metastasis has not been studied clearly. Stearoyl-CoA desaturase 1 (SCD1) is a key enzyme in catalyzing the conversion of saturated fatty acids (SFAs) into monounsaturated fatty acids (MUFAs). SCD1 is overexpressed in breast cancer, and its overexpression is an indicator of poor prognosis in breast cancer patients. However, the role of SCD1 in ErbB2-overexpressing breast cancer metastasis has not been reported. In this study, we investigated the role of SCD1 in the migration and invasion of ErbB2-overexpressing breast cancer cells and its molecular mechanism. First, we demonstrated that ErbB2 upregulates the expression of SCD1. Second, we found that SCD1 and its catalytic product oleic acid played crucial roles in migration and invasion of ErbB2-overexpressing breast cancer cells. Finally, we found that in breast cancer cells, ErbB2 upregulated SCD1 through lactate dehydrogenase A (LDHA). To sum up, upregulation of SCD1 by ErbB2 via LDHA promotes the migration and invasion of breast cancer cells.

Keywords: Breast cancer; ErbB2; LDHA; Migration and invasion; Oleic acid; SCD1.

MeSH terms

  • Breast Neoplasms* / enzymology
  • Breast Neoplasms* / pathology
  • Cell Movement
  • Female
  • Humans
  • Lactate Dehydrogenase 5* / metabolism
  • Neoplasm Invasiveness
  • Receptor, ErbB-2* / genetics
  • Receptor, ErbB-2* / metabolism
  • Stearoyl-CoA Desaturase* / genetics
  • Stearoyl-CoA Desaturase* / metabolism
  • Up-Regulation

Substances

  • ERBB2 protein, human
  • Lactate Dehydrogenase 5
  • Receptor, ErbB-2
  • SCD1 protein, human
  • Stearoyl-CoA Desaturase