KLF15 suppresses stemness of pancreatic cancer by decreasing USP21-mediated Nanog stability.

Autor: Jiang W; Department of Clinical Laboratory, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Hexi District, Huanhuxi Road, Tianjin, 300060, China., Liu L; Department of Clinical Laboratory, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Hexi District, Huanhuxi Road, Tianjin, 300060, China., Wang M; Department of Clinical Laboratory, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Hexi District, Huanhuxi Road, Tianjin, 300060, China., Li X; Department of Pancreatic Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China., Zhou T; Department of Pancreatic Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China., Hou X; Department of Pancreatic Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China., Qiao L; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences of Tianjin Medical University, Tianjin, China., Chen C; Department of Clinical Laboratory, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Hexi District, Huanhuxi Road, Tianjin, 300060, China., Zuo D; Department of Clinical Laboratory, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Hexi District, Huanhuxi Road, Tianjin, 300060, China., Liu J; Department of Breast Oncoplastic Surgery, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, China., Ren L; Department of Clinical Laboratory, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Digestive Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Hexi District, Huanhuxi Road, Tianjin, 300060, China. Ren1999li@163.com.
Jazyk: angličtina
Zdroj: Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2024 Oct 05; Vol. 81 (1), pp. 417. Date of Electronic Publication: 2024 Oct 05.
DOI: 10.1007/s00018-024-05442-6
Abstrakt: The existence of cancer stem cells (CSCs) in pancreatic ductal adenocarcinoma (PDAC) is considered to be the key factor for metastasis and chemoresistance. Thus, novel therapeutic strategies for eradicating CSCs are urgently needed. Here we aimed to explore the role of KLF15 in stemness and the feasibility of using KLF15 to inhibit CSCs and improve chemotherapy sensitivity in PDAC. In this study, we report that KLF15 is negatively associated with poor survival and advanced pathological staging of PDAC. Moreover, tumorous KLF15 suppresses the stemness of PDAC by promoting the degradation of Nanog, and KLF15 directly interacts with Nanog, inhibiting interaction between Nanog with USP21. We also demonstrate that the KLF15/Nanog complex inhibit the stemness in vivo and in PDX cells. Tazemetostat suppresses stemness and sensitizes PDAC cells to gemcitabine by promoting KLF15 expression in PDAC. In summary, the findings of our study confirm the value of KLF15 level in diagnosis and prognosis of PDAC, it is the first time to explore the inhibition role of KLF15 in stemness of PDAC and the regulation mechanism of Nanog, contributing to provide a new therapeutic strategy that using Tazemetostat sensitizes PDAC cells to gemcitabine by promoting KLF15 expression for PDAC.
(© 2024. The Author(s).)
Databáze: MEDLINE
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