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.
[1]Tianjin Med Univ Canc Inst & Hosp, Natl Clin Res Ctr Canc,Dept Clin Lab, Tianjins Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy, Huanhuxi Rd, Tianjin 300060, Peoples R China.
[2]Tianjin Med Univ Canc Inst & Hosp, Natl Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy, Dept Pancreat Canc, Tianjin, Peoples R China.
[3]Tianjin Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Tianjin, Peoples R China.
[4]Tianjin Med Univ Canc Inst & Hosp, Natl Clin Res Ctr Canc, Dept Breast Oncoplast Surg, Key Lab Canc Prevent & Therapy, Tianjin 300060, Peoples R China.
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