LIMK1 promotes the progression of cervical cancer by up-regulating the ROS/Src pathway
Affiliation:

The Fourth Hospital of Hebei Medical University

  • Article
  • | |
  • Metrics
  • |
  • Reference [26]
  • |
  • Related
  • | | |
  • Comments
    Abstract:

    Abstract: Objective To explore the effect of LIMK1 on the progression of cervical cancer (CC). Methods LIMK1-overexpressed human cervical cancer HeLa cells were constructed and inoculated subcutaneously in nude mice. The tumor volume was observed and the expressions of NOX2, NOX4, p-Src, p-RUNX3, RUNX3, and MMP-9 proteins in the tumor cells were detected by Western blot assay. LIMK1-overexpressed HeLa cells were cultured under 5%O2 and added with antioxidants. The protein expressions of LIMK1, NOX4, p-Src, p-RUNX3, RUNX3, and MMP-9 in the cells were detected by Western blot assay. The cell migration ability was detected by scratch assay. Transwell assay was used to detect cell migration and invasion ability. Monoclonal proliferation assay was used to detect cell proliferation ability. Results The tumor volume of nude mice inoculated with LIMK1-overexpressed HeLa cells increased significantly, and NOX2, NOX4, p-Src, p-RUNX3, and MMP-9 proteins increased, while RUNX3 protein expression decreased. In LIMK1-overexpressed HeLa cells, the protein expressions of LIMK1, NOX4, p-Src, p-RUNX3, and MMP-9 were increased, RUNX3 protein expression was decreased, while the cell migration, invasion, and proliferation ability were increased. However, after adding antioxidants, the expression levels of NOX4, p-Src, p-RUNX3, RUNX3, and MMP-9 proteins, and the ability of cell migration, invasion, and proliferation were not different from those of HeLa cells with normal expression of LIMK1. Conclusion LIMK1 promotes the progression of cervical cancer by promoting the ROS/Src pathway, thereby promoting the migration, invasion, and proliferation ability of cervical cancer cells.

    Reference
    [1] Sarah L Bedell,Lena S Doldstein,Amelia R Goldstein,et al.Cervical Cancer Screening: Past, Present, and Future[J].Sex Med Rev,2020 Jan;8(1):28-37.
    [2] David E Gaffney,Mia Hashibe,Deanna Kepka,et al.Too many women are dying from cervix cancer: Problems and solutions[J].Gynecol Oncol,2018 Dec;15(3):547-554.
    [3] Zheng Hu,Ding Ma.The precision prevention and therapy of HPV-related cervical cancer: new concepts and clinical implications[J].Cancer Med,2018 Oct;7(10):5217-5236.
    [4] Patti Olusola,Hirendre Nath Banerjee,Julie V Phillet,et al.Human Papilloma Virus-Associated Cervical Cancer and Health Disparities[J].Cells,2019 Jun 21;8(6):622.
    [5] Paul Gopu,Febin Antony,Sunu Cyriac,et al.Updates on systemic therapy for cervical cancer[J].Indian J Med Res,2021 Aug;154(2):293-302.
    [6] Yuan Liu,Ji-Zheng Guo,Ying Liu,et al.Nuclear lactate dehydrogenase A senses ROS to produce α-hydroxybutyrate for HPV-induced cervical tumor growth[J].Nat Commun,2018 Oct 24;9(1):4429.
    [7] Bruno Rerillo,Marzia Di Donato,Antonio Pezone,et al.ROS in cancer therapy: the bright side of the moon[J].Exp Mol Med,2020 Feb;52(2):192-203.
    [8] Jaewon J Lee,Robert A H van de Ven,Elma Zaganjor,et al.Inhibition of epithelial cell migration and Src/FAK signaling by SIRT3[J].Proc Nati Acad Sci U S A,2018 Jul 3;115(27):7057-7062.
    [9] Juan Luo,Hailin Zou,Yibo Guo,et al.SRC kinase-mediated signaling pathways and targeted therapies in breast cancer[J].Breast Cancer Res,2022 Dec 29;24(1):99.
    [10] Sara G Pelaz,Arantxa Tabernero.Src: coordinating metabolism in cancer[J].Oncogene,2022 Nov;41(45):4917-4928.
    [11] Qiqiao Du,Wei Wang,Tianyu Liu,et al.High Expression of Integrin α3 Predicts Poor Prognosis and Promotes Tumor Metastasis and Angiogenesis by Activating the c-Src/Extracellular Signal-Regulated Protein Kinase/Focal Adhesion Kinase Signaling Pathway in Cervical Cancer[J].Front Oncol,2020 Feb 14;10:36.
    [12] Guojun Lu,Ying Zhou,Chenxi Zhang,et al.Upregulation of LIMK1 Is Correlated With Poor Prognosis and Immune Infiltrates in Lung Adenocarcinoma[J].Front Genet,2021 Jun 3;12:671585.
    [13] Elodie Villalonga,Christine Mosrin,Therry Narmand,et al.LIM Kinases, LIMK1 and LIMK2, Are Crucial Node Actors of the Cell Fate: Molecular to Pathological Features[J].Cells,2023 Mar 4;12(5):805.
    [14] Hua Gong,Lan Zhou,Lotfi Khelfat,et al.Rho-Associated Protein Kinase (ROCK) Promotes Proliferation and Migration of PC-3 and DU145 Prostate Cancer Cells by Targeting LIM Kinase 1 (LIMK1) and Matrix Metalloproteinase-2 (MMP-2)[J].Med Sci Monit,2019 Apr 26;25:3090-3099.
    [15] Xiufang Yang,Huilan Du,Wenhui Bian,et al.FOXD3?AS1/miR?128?3p/LIMK1 axis regulates cervical cancer progression[J].Oncol Rep,2021 May;45(5):62.
    [16] Yongqian Xu,Yujie Zheng,Yan Duan,et al.MicroRNA-125a-5p targets LIM kinase 1 to inhibit cisplatin resistance of cervical cancer cells[J].Oncol Lett,2021 May;21(5):392.
    [17] Yina Qiao,Ting Jin,Shengdong Guan,et al.Long non-coding RNA Lnc-408 promotes invasion and metastasis of breast cancer cell by regulating LIMK1[J].Oncogene,2021 Jun;40(24):4198-4213.
    [18] Xin Liu,Qiang Song,Daohan Wang,et al.LIMK1: A promising prognostic and immune infiltration indicator in colorectal cancer[J].Oncol Lett,2022 May 30;24(1):234.
    [19] Xuecheng Sun,Shaotang Li,Han Lin.LIMK1 Interacts with STK25 to Regulate EMT and Promote the Proliferation and Metastasis of Colorectal Cancer[J].J Oncol,2022 Feb 28;2022:3963883.
    [20] Xi Kang,Weilin Li,Weixin Liu,et al.LIMK1 promotes peritoneal metastasis of gastric cancer and is a therapeutic target[J].Oncogene,2021 May;40(19):3422-3433.
    [21] Serena Castelli,Fabio Ciccarone,Daniela Tavian,et al.ROS-dependent HIF1α activation under forced lipid catabolism entails glycolysis and mitophagy as mediators of higher proliferation rate in cervical cancer cells[J].J Exp Clin Cancer Res,2021 Mar 11;40(1):94.
    [22] Guzal Khayrullina,Sara Bermudez,Deanna Hopkins,et al.Differential effects of NOX2 and NOX4 inhibition after rodent spinal cord injury[J].PLoS One,2023 Mar 10;18(3):e0281045.
    [23] Chih-Chung Liu,Wei-Ning Liu,Rou-Ling Cho,et al.Induction of HO-1 by Mevastatin Mediated via a Nox/ROS-Dependent c-Src/PDGFRα/PI3K/Akt/Nrf2/ARE Cascade Suppresses TNF-α-Induced Lung Inflammation[J].J Clin Med,2020 Jan 15;9(1):226.
    [24] Yun-Mi Goh,Senthilkumar Cinghu,Eileen Tan Hwee Hong,et al.Src kinase phosphorylates RUNX3 at tyrosine residues and localizes the protein in the cytoplasm[J].J Biol Chem,2010 Mar 26;285(13):10122-10129.
    [25] Putthaporn Kaewmeesri, Piman Pocasap,Veerapol Kukongviriyapan,et al.Anti-metastatic Potential of Natural Triterpenoid Cucurbitacin B Against Cholangiocarcinoma Cells by Targeting Src Protein[J].Integr Cancer Ther,2022 Jan-Dec;21:15347354221124861.
    [26] Hao Huang.Matrix Metalloproteinase-9 (MMP-9) as a Cancer Biomarker and MMP-9 Biosensors: Recent Advances[J].Sensors(Basel),2018 Sep 27;18(10):3249.
    Related
    Cited by
Get Citation
Related Videos

Share
Article Metrics
  • Abstract:284
  • PDF: 0
  • HTML: 0
  • Cited by: 0
History
  • Received:September 04,2023
  • Revised:November 13,2023
  • Adopted:February 21,2024
Article QR Code