SIRT1/FOXO Signaling Pathway in Breast Cancer Progression and Metastasis
Makaleler > Tam Makale · 2022
Yazarlar: SAYRA DİLMAÇ, Ayşe CANER, NİLAY KUŞCU, Sendegul Yildirim, ŞÜKRAN BURÇAK YOLDAŞ ÇELİKTEN, Ammad Ahmad Farooqi, GAMZE TANRIÖVER
International Journal of Molecular Sciences, SCI Expanded İndekslerine Giren Dergi, Uluslararası, Wos, 2022, cilt 23, ss 10227-10227
Özet
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.