ARSD is responsible for carcinoma and amyloidosis of breast epithelial cells

Eur J Cell Biol. 2022 Apr;101(2):151199. doi: 10.1016/j.ejcb.2022.151199. Epub 2022 Jan 17.


Breast cancer (BC) and Alzheimer's disease (AD) have pronounced female-to-male disparities and both are the major causes of death in elderly women. Intriguingly, there is an inverse incidence between BC and AD. In our previous study, we found that the expression of ARSD, a female-biased gene on chromosome Xp22.3 that encodes arylsulfatase D, is significantly downregulated in triple-negative breast cancer (TNBC) cells and tissue samples, and that ectopic ARSD overexpression could inhibit proliferation and migration of BC cells. However, the exact mechanism remains unclear. In this study, ARSD-overexpressing MDA-MB-231 cell strains were established. RNA-Seq and qRT-PCR validation were performed followed by GO and KEGG analyses. Transcriptome sequencing unveiled that Alzheimer's/Parkinson's/prion diseases were enriched in ARSD overexpressing BC cells. Besides, the top enriched pathways included lipoprotein/cholesterol metabolism, molecular chaperone and misfolding protein binding, mitochondrial respiration, dysfunction of lysosomes, etc. In which, a battery of genes, e.g., SERF1A, APOE, CD36 etc., were upregulated, while a series of genes, e.g., NDUFA11, NDUFS3, NDUFV1, etc. were downregulated, which were closely related to amyloidosis. The amyloidosis of BC cells and nerval cells caused by ARSD overexpression was verified with western blotting, immunohistochemical and Congo red staining. Collectively, downregulated ARSD may be closely associated with BC, and upregulated ARSD may cause amyloidosis of BC cells. Our findings suggest that ARSD deserves to be considered a new promising target for treating TNBC or for AD.

Keywords: ARSD; Amyloidosis; Breast cancer; Congo red staining; Transcriptome sequencing.

MeSH terms

  • Aged
  • Amyloidosis*
  • Breast Neoplasms* / genetics
  • Carcinoma*
  • Cell Line, Tumor
  • Cell Proliferation
  • Epithelial Cells / pathology
  • Female
  • Humans
  • Male
  • Nerve Tissue Proteins
  • Transcription Factors
  • Triple Negative Breast Neoplasms* / genetics
  • Triple Negative Breast Neoplasms* / pathology


  • Nerve Tissue Proteins
  • SERF1A protein, human
  • Transcription Factors