SIRT1/FOXO Signaling Pathway in Breast Cancer Progression and Metastasis

Abstract

Breast cancer is the second most common cancer in women. The roles of the SIRT and FoxO proteins in tumor progression are known, but their roles in metastasis have not yet been clearly elucidated. In our study, we investigated the roles of SIRT and FoxO proteins their downstream pathways, proteins p21 and p53, in tumor progression and metastasis. We evaluated these proteins in vitro using metastatic 4TLM and 67NR cell lines, as well as their expression levels in tumor-bearing mice. In addition, the regulatory role of SIRT and FoxO proteins in different transduction cascades was examined by IPA core analysis, and clinicopathological evidence was investigated in the TCGA database. In primary tumors, the expression levels of SIRT1, p21, p53, E2F1 and FoxO proteins were higher in 67NR groups. In metastatic tissues, the expression levels of SIRT1, E2F1 and FoxO proteins were found to be enhanced, whereas the levels of p53 and p21 expression were noted to be reduced. IPA analysis also provided empirical evidence of the mechanistic involvement of SIRT and FoxO proteins in tumor progression and metastasis. In conclusion, SIRT1 was found to co-operate with FoxO proteins and to play a critical role in metastasis. Additional research is required to determine why overexpression of SIRT1 in metastatic tissues has oncogenic effects.

The role of LncRNA-MANCR induced by HIF-1a drive the malignant progression of pancreatic cancer by targeting miRNA-494/SIRT1 signaling axis under hypoxic conditions

“…Extensive research indicates that the levels of SIRT1 are elevated in lung, liver, and colon cancers but decreased in pituitary and bladder tumours [50][51][52][53][54] . Despite controversies surrounding SIRT1's role as either a tumour promoter or suppressor, its overexpression has been consistently linked to improvements in EMT.…”

Narrow Leafed Lupin (Lupinus angustifolius L.) β-Conglutin Seed Proteins as a New Natural Cytotoxic Agents against Breast Cancer Cells

“…Whereas, no significant changes were found in the healthy epithelial cell line, MCF-10A, supporting our results describing its resistance to this treatment, at least at the doses used in this report. Recent studies investigated the dual effect of the SIRT1/FoxO1 axis as tumor promotor or suppressor in different cancers [ 58 ], and p53 has emerged as a downstream effector of this axis in BC [ 58 , 59 , 60 ]. Previous results showed that in the MCF-7 cell line, with p53 wild-type, the activation of SIRT1 promoted invasion and migration on malignant cells by inhibiting p53 [ 61 ].…”

“…The SIRT1 signaling pathway plays a key role in the regulation of genes related to metastasis and stemness in BC [ 58 ]. In fact, Shi et al demonstrated that SIRT1-centered circuitry regulates CSCs origination, related to distant-metastasis and drug-resistance in BC [ 26 ].…”

Role of Fork-Head Box Genes in Breast Cancer: From Drug Resistance to Therapeutic Targets

“…In pliable agar, siomycin A had the capacity to slow down the development of cells independent of anchoring. Furthermore, siomycin A selectively induced apoptosis in metamorphosized cells but not in unmetamorphosed cells of similar origin [ 114 ]. Treatment with a cell-permeable ARF26-44 peptide (FOXM1 inhibitor) decreased angiogenesis and tumor cell development and caused a consequential escalation in cell death within the HCC region but not in the surrounding healthy liver tissue.…”