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Triiodothyronine positively regulates endoplasmic reticulum-associated degradation (ERAD) and promotes androgenic signaling in androgen-dependent prostate cancer cells

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dc.creator ERZURUMLU, Yalçın
dc.creator MUHAMMED, Muhammed Tılahun
dc.date 2023-09-01T00:00:00Z
dc.date.accessioned 2025-02-25T10:41:07Z
dc.date.available 2025-02-25T10:41:07Z
dc.identifier edc303cf-88a3-4087-9290-9bcd6aa760b8
dc.identifier 10.1016/j.cellsig.2023.110745
dc.identifier https://avesis.sdu.edu.tr/publication/details/edc303cf-88a3-4087-9290-9bcd6aa760b8/oai
dc.identifier.uri http://acikerisim.sdu.edu.tr/xmlui/handle/123456789/101846
dc.description Thyroid hormones (THs) play crucial roles in numerous physiological processes of nearly all mammalian tissues, including differentiation and metabolism. Deterioration of TH signaling has been associated with several pathologies, including cancer. The effect of highly active triiodothyronine (T3) has been investigated in many in vivo and in vitro cancer models. However, the role of T3 on cancerous prostate tissue is controversial today. Recent studies have focused on the characterization of the supportive roles of the endoplasmic reticulum-associated degradation (ERAD) and unfolded protein response (UPR) signaling in prostate cancer (PCa) and investigating new hormonal regulation patterns, including estrogen, progesterone and 1,25(OH)2D3. Additionally, androgenic signaling controlled by androgens, which are critical in PCa progression, has been shown to be regulated by other steroid hormones. Today, the effects of T3 on ERAD and UPR are unknown, the impact on androgenic signaling is also still not fully understood in PCa. Therefore, we aimed to investigate the molecular action of T3 on the ERAD mechanism and UPR signaling in PCa cells and also extensively examined the effect of T3 on androgenic signaling. Our data indicated that T3 tightly regulated ERAD and UPR signaling in androgen-dependent PCa cells. We also found that T3 hormone stimulated androgenic signaling by upregulating AR mRNA and protein levels and enhancing its nuclear translocation. Additionally, advanced computational studies supported the ligand binding effect of T3 on AR protein. Our data suggest that targeting thyroidal signaling should be considered in therapeutic approaches to be developed for prostate malignancy in addition to other steroidal regulations.
dc.language eng
dc.rights info:eu-repo/semantics/closedAccess
dc.title Triiodothyronine positively regulates endoplasmic reticulum-associated degradation (ERAD) and promotes androgenic signaling in androgen-dependent prostate cancer cells
dc.type info:eu-repo/semantics/article


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