Doxycycline Inhibits Cancer Stem Cell-Like Properties via PAR1/FAK/PI3K/AKT Pathway in Pancreatic Cancer

被引：19
|
作者：
Liu, Huijuan [1 ,2 ,3 ,4 ]
Tao, Honglian [1 ,2 ,3 ]
Wang, Hongqi [1 ,2 ,3 ]
Yang, Yuyan [1 ,2 ,3 ]
Yang, Ru [1 ,2 ,3 ]
Dai, Xintong [1 ,2 ,3 ]
Ding, Xiujuan [1 ,2 ,3 ]
Wu, Haidong [3 ]
Chen, Shuang [3 ]
Sun, Tao [1 ,2 ,3 ,5 ]
机构：
[1] Nankai Univ, State Key Lab Med Chem Biol, Tianjin, Peoples R China
[2] Nankai Univ, Coll Pharm, Tianjin, Peoples R China
[3] Tianjin Int Joint Acad Biomed, Tianjin Key Lab Early Druggabil Evaluat Innovat D, Tianjin, Peoples R China
[4] Tianjin Third Cent Hosp, Tianjin Key Lab Extracorporeal Life Support Crit, Tianjin, Peoples R China
[5] Tianjin Med Univ, Tianjin Inst Digest Dis, Gen Hosp, Dept Gastroenterol & Hepatol, Tianjin, Peoples R China
来源：
FRONTIERS IN ONCOLOGY | 2021年 / 10卷
关键词：
protease activation receptor 1; focal adhesion kinase; doxycycline; epithelial– mesenchymal transformation; pancreatic cancer stem cells; FAK;
D O I：
10.3389/fonc.2020.619317
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Pancreatic cancer stem cells (CSCs) play an important role in the promotion of invasion and metastasis of pancreatic cancer. Protease activation receptor 1 (PAR1) is closely related to malignant progression of tumors, however, its effects on pancreatic cancer stem cell-like (CSC-like) properties formation have not been reported. In this work, the effects of PAR1 on pancreatic cancer stem cell-like (CSC-like) properties formation were studied. PAR1 overexpression can induce CSC-like properties in Aspc-1 cells, whereas interference of PAR1 in Panc-1 cells showed the contrary results. Data on patients with pancreatic cancer obtained from TCGA showed that high PAR1 expression and focal adhesion kinase (FAK) protein considerably affect the prognosis of patients. Further experiments showed that PAR1 could regulate FAK, PI3K, and AKT phosphorylation and the epithelial-mesenchymal transformation (EMT) in Aspc-1 and Panc-1 cells. Doxycycline, as a PAR1 inhibitor, could effectively inhibit the CSC-like properties of pancreatic cancer cells and the FAK/PI3K/AKT pathway activation. Doxycycline inhibits the growth of pancreatic cancer and enhances the treatment effect of 5-fluorouracil (5-FU) in Panc-1 xenograft mouse model. In conclusion, PAR1 promotes the CSC-like properties and EMT of pancreatic cancer cells via the FAK/PI3K/AKT pathway. Doxycycline inhibits the pancreatic cancer through the PAR1/FAK/PI3K/AKT pathway and enhances the therapeutic effect of 5-FU.
引用
收藏
页数：12
相关论文
共 50 条
  • [11] SPOCD1 accelerates ovarian cancer progression and inhibits cell apoptosis via the PI3K/AKT pathway
    Liu, Dajiang
    Yang, Yuan
    Yan, Aiqin
    Yang, Yongxiu
    ONCOTARGETS AND THERAPY, 2020, 13 : 351 - 359
  • [12] DTX3L Accelerates Pancreatic cancer Progression via FAK/PI3K/AKT Axis
    Liang Chen
    Wenyang Niu
    Hong Zang
    Yudong Qiu
    Biochemical Genetics, 2024, 62 : 814 - 830
  • [13] DTX3L Accelerates Pancreatic cancer Progression via FAK/PI3K/AKT Axis
    Chen, Liang
    Niu, Wenyang
    Zang, Hong
    Qiu, Yudong
    BIOCHEMICAL GENETICS, 2024, 62 (02) : 814 - 830
  • [14] Osteopontin Promotes Colorectal Cancer Cell Invasion and the Stem Cell-Like Properties through the PI3K-AKT-GSK/3β-β/Catenin Pathway
    Cheng, Yuanguang
    Wen, Gang
    Sun, Yong
    Shen, Yang
    Zeng, Yongqing
    Du, Ming
    Zhu, Guangyu
    Wang, Guangtong
    Meng, Xiangling
    MEDICAL SCIENCE MONITOR, 2019, 25 : 3014 - 3025
  • [15] Prospects of targeting PI3K/AKT/mTOR pathway in pancreatic cancer
    Mortazavi, Motahareh
    Moosavi, Fatemeh
    Martini, Miriam
    Giovannetti, Elisa
    Firuzi, Omidreza
    CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 2022, 176
  • [16] Obesity and pancreatic cancer: Possible role of the PI3K/Akt pathway
    Huang, Xu-Feng
    Chen, Jiezhong
    SURGERY, 2010, 147 (04) : 596 - 596
  • [17] Picropodophyllin inhibits type I endometrial cancer cell proliferation via disruption of the PI3K/Akt pathway
    Dong, Lin
    Du, Meirong
    Lv, Qianzhou
    ACTA BIOCHIMICA ET BIOPHYSICA SINICA, 2019, 51 (07) : 753 - 760
  • [18] Precancerous keratinocytes promote neighboring HNSCC cancer stem cell-like properties and PI3K inhibitor insensitivity via EGFR
    Nguyen, Khoa A.
    Keith, Madison J.
    Wang, Xiao-Jing
    Young, Christian D.
    CANCER RESEARCH, 2019, 79 (13)
  • [19] Activation of glucagon-like peptide-1 receptor inhibits tumourigenicity and metastasis of human pancreatic cancer cells via PI3K/Akt pathway
    Zhao, H.
    Wang, L.
    Wei, R.
    Xiu, D.
    Tao, M.
    Ke, J.
    Liu, Y.
    Yang, J.
    Hong, T.
    DIABETES OBESITY & METABOLISM, 2014, 16 (09): : 850 - 860
  • [20] PABPC1 Silencing Inhibits Gastric Cancer Cell Proliferation, Metastasis, and EMT Via the PI3K/AKT Pathway
    Fang, Jun
    Zhang, Qiong
    Wang, Qingrui
    BIOCHEMICAL GENETICS, 2024,
12345