Serum amyloid A1: Innocent bystander or active participant in cell migration in triple-negative breast cancer?

Exp Cell Res. 2021 Sep 1;406(1):112759. doi: 10.1016/j.yexcr.2021.112759. Epub 2021 Jul 29.

Abstract

The Serum Amyloid A (SAA) family of proteins is associated with various pathological conditions, including cancer. However, their role in cancer is incompletely understood. Here, we investigated the role of SAA1 in cell cycle regulation, apoptosis, survival signaling, metabolism, and metastasis in models of triple-negative breast cancer (TNBC), using RNAi. Our data show that in untransformed epithelial cells (MCF12A), the knockdown of SAA1 induces the expression of cell cycle regulators (MCM2, p53), the activation of DNA repair (PARP synthesis), and survival signaling (NFκB). In contrast, knockdown of SAA1 in the TNBC cell line (MDA-MB-231) induced the expression p16 and shifted cells in the cell cycle from the S to G2/M phase, without the activation of DNA repair. Moreover, in SAA1-deficient MDA-MB-231 and HCC70 cells, metabolism (NADH oxidation) continually increased while cell migration (% wound closure and the rate of wound closure) decreased. However, silencing of SAA1 altered epithelial and mesenchymal markers in MCF12A (E-cadherin, Laminin 1β, Vimentin) and MDA-MB-231 (α-Smooth muscle actin) cells, associated with the metastatic program of epithelial-mesenchymal transition. Nonetheless, our data provide evidence that SAA1 could potentially serve as a therapeutic target in TNBC.

Keywords: Apoptosis; Breast cancer; Cell cycle; Metastasis; Serum amyloid A1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Apoptosis / genetics*
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Cycle / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Laminin / genetics
  • Laminin / metabolism
  • Minichromosome Maintenance Complex Component 2 / genetics
  • Minichromosome Maintenance Complex Component 2 / metabolism
  • Models, Biological
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Serum Amyloid A Protein / antagonists & inhibitors
  • Serum Amyloid A Protein / genetics*
  • Serum Amyloid A Protein / metabolism
  • Signal Transduction
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Vimentin / genetics
  • Vimentin / metabolism

Substances

  • ACTA2 protein, human
  • Actins
  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • Cyclin-Dependent Kinase Inhibitor p16
  • Laminin
  • NF-kappa B
  • RNA, Small Interfering
  • SAA1 protein, human
  • Serum Amyloid A Protein
  • Tumor Suppressor Protein p53
  • VIM protein, human
  • Vimentin
  • laminin 1
  • Poly(ADP-ribose) Polymerases
  • MCM2 protein, human
  • Minichromosome Maintenance Complex Component 2