SODD Promotes Lung Cancer Tumorigenesis by Activating the PDK1/AKT and RAF/MEK/ERK Signaling

被引:1
|
作者
Bao, Fan [1 ,2 ]
An, Su [2 ]
Yang, Yang [2 ]
Xu, Tian-Rui [2 ]
机构
[1] Kunming Univ Sci & Technol, Fac Environm Sci & Engn, 727 Jingming South Rd, Kunming 650500, Peoples R China
[2] Kunming Univ Sci & Technol, Fac Life Sci & Technol, Kunming 650500, Peoples R China
关键词
SODD; gene knockout; PDK1; AKT; MAPK; lung cancer; 3-PHOSPHOINOSITIDE-DEPENDENT PROTEIN KINASE-1; MAMMARY EPITHELIAL-CELLS; DEATH; EXPRESSION; SILENCER; PATHWAY; BAG-1; INHIBITION; APOPTOSIS; FAMILY;
D O I
10.3390/genes14040829
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Background: The Bcl2-associated athanogene4 (BAG4/SODD) protein could be identified as a tumor marker for several malignancies and plays a major role in the occurrence, development, and drug resistance of tumors. However, the role of Silencer of death domains (SODD) in lung carcinogenesis is still elusive. Objective: To illuminate the effect of SODD on the proliferation, migration, invasion, and apoptosis of lung cancer cells and tumor growth in vivo and explore the corresponding mechanism. Methods: The expression of SODD in tumor and normal tissues was determined and compared via western blot. SODD gene knockout lung cancer cells (H1299 cells) were established through a CRISPR/Cas9 gene deleting system, and a transient SODD overexpression of H1299 cells was also constructed. Then, cell proliferation and invasion were assessed through colony formation and cell counting kit-8 assays, transwell migration assays, and wound healing assays. Cell drug sensitivity is also analyzed by Cell Counting Kit-8 assay. The flow cytometer was used to perform cell circle and apoptosis analysis. The interaction of SODD and RAF-1 was confirmed by co-immunoprecipitation, and the phosphorylated level of Phosphatidylinositol 3-kinase (PI3K), Serine/threonine-protein kinase (AKT), Rapidly accelerated fibrosarcoma (RAF)-1,and extracellular signal regulated kinase (ERK) in cells was examined by western blot to evaluate the activation of PI3K/PDK1/AKT and RAF/MEK/ERK pathways. In vivo, Xenograft tumor assay of SODD knockout H1299 cells was used to evaluate further the role of SODD on the proliferation of H1299 cells. Results: SODD binds to RAF-1 and is over-expressed in lung tissues, and promotes the proliferation, migration, invasion, and drug sensitivity of H1299 cells. The reduced cells in the S phase and increased cells arrested in the G2/M phase were found in SODD knockout H1299 cells, and more cells got apoptosis. The expression of 3-phosphoinositide-dependent protein kinase 1(PDK1) protein in SODD knockout H1299 cells decreases distinctively, and the phosphorylated level of AKT, RAF-1, and ERK-1 kinase in SODD knockout H1299 cells is also less than that in normal H1299 cells. In contrast, SODD overexpression significantly increases the phosphorylation of AKT. In vivo, SODD promotes the tumorigenicity of H1299 cells in nude mice. Conclusions: SODD is overexpressed in lung tissues and plays a considerable role in the development and progression of lung cancer by regulating the PI3K/PDK1/AKT and RAF/MEK/ERK pathways.
引用
收藏
页数:13
相关论文
共 50 条
  • [1] A Novel PDK1/MEK Dual Inhibitor Induces Cytoprotective Autophagy via the PDK1/Akt Signaling Pathway in Non-Small Cell Lung Cancer
    Liu, Rangru
    Chen, Zhuo
    Hu, Gaoyun
    Yu, Zutao
    Li, Qianbin
    Liu, Danqi
    Li, Ling
    Liu, Zhaoqian
    PHARMACEUTICALS, 2023, 16 (02)
  • [2] TCF19 promotes cell proliferation and tumor formation in lung cancer by activating the Raf/MEK/ERK signaling pathway
    Tian, Yahui
    Xin, Shaowei
    Wan, Zitong
    Dong, Honghong
    Liu, Lu
    Fan, Zhenzhen
    Li, Tian
    Peng, Fujun
    Xiong, Yanlu
    Han, Yong
    TRANSLATIONAL ONCOLOGY, 2024, 45
  • [3] Crosstalk between PI3 Kinase/PDK1/Akt/Rac1 and Ras/Raf/MEK/ERK Pathways Downstream PDGF Receptor
    Niba, Emma Tabe Eko
    Nagaya, Hisao
    Kanno, Takeshi
    Tsuchiya, Ayako
    Gotoh, Akinobu
    Tabata, Chiharu
    Kuribayashi, Kohzo
    Nakano, Takashi
    Nishizaki, Tomoyuki
    CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2013, 31 (06) : 905 - 913
  • [4] Timp1 Promotes Cell Survival by Activating the PDK1 Signaling Pathway in Melanoma
    Toricelli, Mariana
    Melo, Fabiana H. M.
    Hunger, Aline
    Zanatta, Daniela
    Strauss, Bryan E.
    Jasiulionis, Miriam G.
    CANCERS, 2017, 9 (04)
  • [5] SD-2102, a novel PDK1 inhibitor, suppresses lung cancer growth by interrupting PDK1/Akt pathway
    Park, Seyong
    Namgung, Hee
    Om, Darlami
    Kang, Juhee
    Jung, Hyunjin
    Shin, Dongyun
    Oh, Seunghyun
    CANCER SCIENCE, 2023, 114 : 1255 - 1255
  • [6] Low protein expression of LZTR1 in hepatocellular carcinoma triggers tumorigenesis via activating the RAS/RAF/MEK/ ERK signaling
    Ye, Ganghui
    Wang, Jie
    Xia, Jingyi
    Zhu, Chenlu
    Gu, Chaoyu
    Li, Xinming
    Li, Jingyun
    Ye, Meng
    Jin, Xiaofeng
    HELIYON, 2024, 10 (12)
  • [7] The Deacetylase SIRT1 Promotes Membrane Localization and Activation of Akt and PDK1 During Tumorigenesis and Cardiac Hypertrophy
    Sundaresan, Nagalingam R.
    Pillai, Vinodkumar B.
    Wolfgeher, Don
    Samant, Sadhana
    Vasudevan, Prabhakaran
    Parekh, Vishwas
    Raghuraman, Hariharasundaram
    Cunningham, John M.
    Gupta, Madhu
    Gupta, Mahesh P.
    SCIENCE SIGNALING, 2011, 4 (182)
  • [8] RIPK4/PEBP1 axis promotes pancreatic cancer cell migration and invasion by activating RAF1/MEK/ERK signaling
    Qi, Zi-Hao
    Xu, Hua-Xiang
    Zhang, Shi-Rong
    Xu, Jin-Zhi
    Li, Shuo
    Gao, He-Li
    Jin, Wei
    Wang, Wen-Quan
    Wu, Chun-Tao
    Ni, Quan-Xing
    Yu, Xian-Jun
    Liu, Liang
    INTERNATIONAL JOURNAL OF ONCOLOGY, 2018, 52 (04) : 1105 - 1116
  • [9] RUVBL1, a novel C-RAF-binding protein, activates the RAF/MEK/ERK pathway to promote lung cancer tumorigenesis
    Guo, Hui
    Zhang, Xin-Yu
    Peng, Jun
    Huang, Ying
    Yang, Yang
    Liu, Ying
    Guo, Xiao-Xi
    Hao, Qian
    An, Su
    Xu, Tian-Rui
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2018, 498 (04) : 932 - 939
  • [10] PDK1: At the crossroad of cancer signaling pathways
    Gagliardi, Paolo Armando
    Puliafito, Alberto
    Primo, Luca
    SEMINARS IN CANCER BIOLOGY, 2018, 48 : 27 - 35