The Adipokine Visfatin Modulates Cancer Stem Cell Properties in Triple-Negative Breast Cancer

Abstract

Obesity is a cancer progression risk factor; excessive adipocytes increase adipokine secretion. Visfatin, a novel adipokine highly expressed in cancer patients, is related to breast cancer risk. The modulation of nicotinamide adenine dinucleotide (NAD+) metabolism and the induction of a tumorigenic environment plays a vital role in cancer progression. Among cancer cell types, cancer stem-like cells (CSCs) with self-renewal and chemotherapy-resistance abilities could modulate tumor progression and cancer recurrence ability. In this study, we focused on visfatin’s modulation effect on stemness-related properties using the high-malignancy breast cancer cell line MDA-MB-231 in in vitro and in vivo studies. Visfatin treatment significantly increased both the sphere number and sphere diameter and increased the protein expression of NANOG homeobox (NANOG), sex-determining region Y-box 2 (SOX2), and octamer-binding transcription factor 4 (OCT4), as well as SIRT1 protein levels. The serum angiogenesis marker VEGF and extracellular nicotinamide phosphoribosyl transferase (NAMPT, visfatin) were induced after visfatin treatment, increasing the stemness and angiogenesis environment, which were significantly reduced by the visfatin inhibitor FK866. Our results demonstrate that the visfatin-activated SIRT–SOX2 axis promotes triple-negative breast cancer stemness and enriches the tumorigenic microenvironment.

Hinokitiol Inhibits Breast Cancer Cells In Vitro Stemness-Progression and Self-Renewal with Apoptosis and Autophagy Modulation via the CD44/Nanog/SOX2/Oct4 Pathway

“…CD44 is a cell surface glycoprotein that plays a critical role in cell adhesion, cell migration, and cancer cell invasion. It is also a well-known stem cell marker that has been implicated in stemness regulation and cancer stem cells development [36]. Nanog is involved in cancer cell self-renewal regulation and differentiation, while SOX2 and Oct4 are involved in the maintenance of pluripotency in embryonic stem cells [37].…”

Adipocyte regulation of cancer stem cells

“…Adipokine visfatin increases stemness and angiogenesis in breast cancer. Visfatin enhances tumor sphere formation and protein expression levels of the stem cell genes NANOG, SOX2, OCT4, and Sirtuin 1 (SIRT1), which is diminished by the visfatin inhibitor FK866 61 …”