|Table of Contents|

PAK2 promotes cisplatin resistance in lung cancer cells by regulating the activity of ERK signaling pathway

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 13
Page:
2448-2454
Research Field:
Publishing date:

Info

Title:
PAK2 promotes cisplatin resistance in lung cancer cells by regulating the activity of ERK signaling pathway
Author(s):
WANG Shuang1RONG Xuezhu2WANG Si3LI Zhen2LIU Yang2
1.Department of Anesthesiology;2.Department of Pathology,The First Hospital of China Medical University,Liaoning Shenyang 110001,China;3.Department of Medical Microbiology and Human Parasitology,Basic Medicine College,China Medical University,Liaoning Shenyang 110122,China.
Keywords:
NSCLCp21-activated kinase 2cell proliferationcell invasionERK signal pathway
PACS:
R734.2
DOI:
10.3969/j.issn.1672-4992.2023.13.014
Abstract:
Objective:To investigate the expression pattern of p21 activated kinase 2(PAK2) in non-small cell lung cancer(NSCLC) and its effect on the proliferation and invasion of lung cancer cells.Methods:The protein expression level of PAK2 in NSCLC was detected by immunohistochemistry and Western blot(WB).PAK2-siRNA was used to down-regulate the expression of PAK2 in lung cancer cell lines.We revealed the effects of PAK2 on the cell malignant phenotype and the possible molecular regulation mechanisms via WB and cell function experiments.In the process of inducing the erlotinib resistance of lung cancer cell lines,the expression level of PAK2 and its effect on erlotinib sensitivity were also detected.Results:Compared with normal lung tissues,PAK2 showed strong cytoplasmic expression in NSCLC,and its abnormal expression was correlated with low differentiation(P=0.014),high TNM stage(P=0.011) and lymph node metastasis(P=0.040).In lung cancer cell lines,PAK2 down-regulation significantly inhibited the proliferation(P<0.05) and invasion(P<0.05) of lung cancer cells by inhibiting the activity of ERK signaling pathway.Furthermore,PAK2 down-regulation promote the sensitivity of lung cancer cells to erlotinib.Conclusion:PAK2 plays an important role in promoting oncogene function in NSCLC,and plays an important role in mediating drug resistance of NSCLC,which is expected to provide scientific basis for seeking individualized treatment of NSCLC.

References:

[1] RANE CK,MINDEN A.p21 activated kinase signaling in cancer [J].Semin Cancer Biol,2019,54(1):40-49.
[2] WANG Y,GUO FH.Group I PAKs in myelin formation and repair of the central nervous system:what,when,and how [J].Biological Reviews of the Cambridge Philosophical Society,2022,97(2):615-639.
[3] LIU H,LIU KD,DONG ZG.The role of p21-activated kinases in cancer and beyond:Where are we heading [J].Frontiers in Cell and Developmental Biology,2021,9(1):641381-641382.
[4] MONTALTO FI,DE AMICIS F.Cyclin D1 in cancer:A molecular connection for cell cycle control,adhesion and invasion in tumor and stroma [J].Cells,2020,9(12):2648-2649.
[5] RAMOS-GARCIA P,GIL-MONTOYA JA,SCULLY C,et al.An update on the implications of cyclin D1 in oral carcinogenesis [J].Oral Dis,2017,23(7):897-912.
[6] RADENKOVIC S,KONJEVIC G,NIKITOVIC M,et al.Evaluation of Cyclin D1 expression by western blotting methods and immunohistochemistry in breast cancer patients [J].Journal of Buon,2021,26(2):475-482.
[7] CHU C,GENG Y,ZHOU Y,et al.Cyclin E in normal physiology and disease states [J].Trends Cell Biol,2021,31(9):732-746.
[8] PANG W,LI Y,GUO W,et al.Cyclin E:a potential treatment target to reverse cancer chemoresistance by regulating the cell cycle [J].Am J Transl Res,2020,2(9):5170-5187.
[9] CARUSO JA,DUONG MT,CAREY JPW,et al.Low-molecular-weight cyclin E in human cancer:Cellular consequences and opportunities for targeted therapies [J].Cancer Res,2018,78(19):5481-5491.
[10] LIU DG,KANG HX,GAO MT,et al.Exosome-transmitted circ_MMP2 promotes hepatocellular carcinoma metastasis by upregulating MMP2 [J].Mol Oncol,2020,14(6):1365-1380.
[11] YAN Y,FANG LI,LI YX,et al.Association of MMP2 and MMP9 gene polymorphisms with the recurrent spontaneous abortion:A meta-analysis [J].Gene,2021,767(1):145173-145174.
[12] JIANG H,LI H.Prognostic values of tumoral MMP2 and MMP9 overexpression in breast cancer:a systematic review and meta-analysis [J].BMC Cancer,2021,21(1):149-150.
[13] SANYAL S,AMIN SA,ADHIKARI N,et al.Ligand-based design of anticancer MMP2 inhibitors:a review [J].Future Med Chem,2021,13(22):1987-2013.
[14] WANG X,YANG B,SHE Y,et al.The lncRNA TP73-AS1 promotes ovarian cancer cell proliferation and metastasis via modulation of MMP2 and MMP9 [J].J Cell Biochem,2018,119(9):7790-7799.
[15] JOSEPH C,ALSALEEM M,ORAH N,et al.Elevated MMP9 expression in breast cancer is a predictor of shorter patient survival [J].Breast Cancer Res Treat,2020,182(2):267-282.
[16] MONDAL S,ADHIKARI N,BANERJEE S,et al.Matrix metalloproteinase-9(MMP-9) and its inhibitors in cancer:A minireview [J].Eur J Med Chem,2020,194(1):112260-112261.
[17] AKULA SM,ABRAMS SL,STEELMAN LS,et al.RAS/RAF/MEK/ERK,PI3K/PTEN/AKT/mTORC1 and TP53 pathways and regulatory miRs as therapeutic targets in hepatocellular carcinoma [J].Expert Opin Ther Targets,2019,23(11):915-929.
[18] MAZEIN A,ROUGNY A,KARR JR,et al.Reusability and composability in process description maps:RAS-RAF-MEK-ERK signaling [J].Brief Bioinform,2021,22(5):103-104.
[19] HAN J,LIU Y,YANG S,et al.MEK inhibitors for the treatment of non-small cell lung cancer [J].J Hematol Oncol,2021,14(1):1-2.
[20] WEN Z,JIANG R,HUANG Y,et al.Inhibition of lung cancer cells and Ras/Raf/MEK/ERK signal transduction by ectonucleoside triphosphate phosphohydrolase-7(ENTPD7) [J].Respir Res,2019,20(1):194-195.
[21] ROSKOSKI R JR.Targeting oncogenic Raf protein-serine/threonine kinases in human cancers [J].Pharmacol Res,2018,135(1):239-258.

Memo

Memo:
National Natural Science Foundation of China(No.82003119);国家自然科学基金(编号:82003119);辽宁省教育厅高校基本科研项目(编号:LJKZ0763)
Last Update: 2023-05-31