|
|
Study of the role and mechanism of C-terminal Src protein / focal adhesion kinase / E-cadherin pathway in invasion and metastasis of cervical cancer |
TANG Qunhua MU Xiaoqin HUANG Shilan TANG Zhikang LIAN Xiaoling▲ |
Department of Gynecology, the First Affiliated Hospital of Hunan University of Medicine, Hunan Province, Huaihua 418000, China
|
|
|
Abstract Objective To study the role and mechanism of C-terminal Src protein (c-Src) / focal adhesion kinase (FAK) / E-cadherin (E-cad) pathway in invasion and metastasis of cervical cancer. Methods Thirty cervical squamous cell carcinoma (CSCC) tissue samples and 30 normal cervical (NC) tissue samples were collected from the First Affiliated Hospital of Hunan University of Medicine from January 2019 to December 2020. Immunohistochemical stain was used to detect the positive rate of E-cad in CSCC and NC tissue samples. The relationship between E-cad and clinicopathological features of CSCC patients was analyzed. Western blot was used to detect the protein expression levels of c-Src, FAK, and E-cad in CSCC and NC tissues. In addition, cervical cancer Caski cell lines were selected and divided into Caski group and Caski+ c-SRC inhibitor group. The Caski group was not treated, and the Caski+c-SRC inhibitor group was added with c-Src inhibitor (2.7 nmol/L). The migration, invasion, and apoptosis of the two groups were observed, and the protein expression levels of c-Src, FAK, and E-cad in the two groups were detected by Western blot. Results The positive rate of E-cad in CSCC tissue samples was lower than that in NC, the difference was statistically significant (P < 0.05). E-cad expression was correlated with International Federation of Gynecology and Obstetrics staging, differentiation degree, and recurrence of CSCC patients (P < 0.05). The expression levels of c-Src and FAK protein in CSCC tissue samples were higher than those in NC tissue samples, while the expression level of E-cad protein was lower than that in NCT, the differences were statistically significant (P < 0.05). The count of invaded and migrated cells and the expression levels of c-Src and FAK protein in Caski+c-Src inhibitor group were lower than those in Caski group, and the apoptosis rate and expression level of E-cad protein were higher than those in Caski group, the differences were statistically significant (P < 0.05). Conclusion C-src may lead to decreased invasion and migration ability of cervical cancer cells by up-regulating FAK and down-regulating E-cad, the mechanism may be related to increased apoptosis.
|
|
|
|
|
[1] 高丽君,成龙,刘霄,等.新辅助化疗对Ⅰ、Ⅱ期宫颈癌患者预后的Meta分析[J].中国医药导报,2017,14(8):102-106,119.
[2] Xie L,Chu R,Wang K,et al. Prognostic Assessment of Cervical Cancer Patients by Clinical Staging and Surgical-Pathological Factor:A Support Vector Machine-Based Approach [J]. Front Oncol,2020,10:1353.
[3] Padmanaban V,Krol I,Suhail Y,et al. E-cadherin is required for metastasis in multiple models of breast cancer [J]. Nature,2019,573(7774):439-444.
[4] Na TY,Schecterson L,Mendonsa AM,et al. The functional activity of E-cadherin controls tumor cell metastasis at multiple steps [J]. Proc Natl Acad Sci U S A,2020,117(11):5931-5937.
[5] Hong X,Yu JJ. Silencing of lysyl oxidase-like 2 inhibits the migration,invasion and epithelial to mesenchymal transition of renal cell carcinoma cells through the Src/FAK signaling pathway [J]. Int J Oncol,2019,54(5):1676-1690.
[6] Ma H,Wang J,Zhao X,et al. Periostin Promotes Colorectal Tumorigenesis through Integrin-FAK-Src Pathway-Mediated YAP/TAZ Activation [J]. Cell Rep,2020,30(3):793-806.
[7] Green TP,Fennell M,Whittaker R,et al. Preclinical anticancer activity of the potent,oral Src inhibitor AZD0530 [J]. Mol Oncol,2009,3(3):248-261.
[8] 安淑香,孙硼朋,徐锦江.LAD1在结直肠肿瘤中的表达及临床意义[J].诊断病理学杂志,2021,28(6):465-468.
[9] 王正栋,陆翠华,沈小建,等.CAⅨ、E-cadherin和β-catenin在胃癌组织中的表达及意义[J].中国临床研究,2020,33(10):1358-1362.
[10] 马宇光,张寅斌,昝瑛,等.膀胱移行细胞癌组织中沉默信息调节因子2相关酶1和E钙黏附素的表达及其相关性[J].中国医药,2020,15(11):1744-1748.
[11] 朱平,梁欣泉,廖欣,等.吡柔比星调控原钙黏蛋白10的表达对多发性骨髓瘤细胞增殖、凋亡诱导的作用机制研究[J].疑难病杂志,2020,19(2):184-189.
[12] 何丽娜,许剑利,张雨涛,等.人角化层糜蛋白酶及E钙粘蛋白在宫颈癌中的表达及意义[J].中国妇幼保健,2017,32(13):3032-3035.
[13] Chang CH,Chen MC,Chiu TH,et al. Arecoline Promotes Migration of A549 Lung Cancer Cells through Activating the EGFR/Src/FAK Pathway [J]. Toxins(Basel),2019,11(4):185.
[14] Ji Z,Su J,Hou Y,et al. EGFR/FAK and c-Src signaling pathways mediate the internalization of Staphylococcus aureus by osteoblasts [J]. Cell Microbiol,2020,22(10):e13240.
[15] Higuchi M,Ishiyama K,Maruoka M,et al. Paradoxical activation of c-Src as a drug-resistant mechanism [J]. Cell Rep,2021,34(12):108876.
[16] Mayoral V,Sánchez MP,Calcabrini A,et al. The Relevance of the SH2 Domain for c-Src Functionality in Triple-Negative Breast Cancer Cells [J]. Cancers(Basel),2021, 13(3):462.
[17] Pelaz SG,Jaraíz M,?譧lvarez A,et al. Targeting metabolic plasticity in glioma stem cells in vitro and in vivo through specific inhibition of c-Src by TAT-Cx43266-283 [J]. EBioMedicine,2020,62:103134.
[18] Song X,Xu H,Wang P,et al. Focal adhesion kinase(FAK)promotes cholangiocarcinoma development and progression via YAP activation [J]. J Hepatol,2021,75(4):888-899.
[19] Lv PC,Jiang AQ,Zhang WM,et al. FAK inhibitors in Cancer,a patent review [J]. Expert Opin Ther Pat,2018, 28(2):139-145.
[20] Chang CH,Chen MC,Chiu TH,et al. Arecoline Promotes Migration of A549 Lung Cancer Cells through Activating the EGFR/Src/FAK Pathway [J]. Toxins(Basel),2019,11(4):185.
[21] Huang CC,Tseng TT,Liu SC,et al. S1P Increases VEGF Production in Osteoblasts and Facilitates Endothelial Progenitor Cell Angiogenesis by Inhibiting miR-16-5p Expression via the c-Src/FAK Signaling Pathway in Rheumatoid Arthritis [J]. Cells,2021,10(8):2168.
[22] Abula Y,Su Y,Tuniyazi D,et al. Desmoglein 3 contributes to tumorigenicity of pancreatic ductal adenocarcinoma through activating Src-FAK signaling [J]. Anim Cells Syst(Seoul),2021,25(3):195-202.
[23] Sáenz I,Celada L,San A,et al. Blockage of Squamous Cancer Cell Collective Invasion by FAK Inhibition Is Released by CAFs and MMP-2 [J]. Cancers(Basel),2020,12(12):3708.
[24] Liu J,Xue L,Xu X,et al. FAK-Targeting PROTAC Demonstrates Enhanced Antitumor Activity against KRAS Mutant Non-Small Cell Lung Cancer [J]. Exp Cell Res,2021,408(2):112868.
[25] Liu Y,Li L,Liu X,et al. Retraction:Arginine methylation of SHANK2 by PRMT7 promotes human breast cancer metastasis through activating endosomal FAK signalling [J]. Elife,2021,10:e72188.
[26] Xu J,Zhang W. EZR promotes pancreatic cancer proliferation and metastasis by activating FAK/AKT signaling pathway [J]. Cancer Cell Int,2021,21(1):521.
[27] 罗华荣,王天如,陈晨,等.ROS/SRC/FAK信号通路在膀胱癌疾病进展中的作用机制研究[J].疑难病杂志,2021,20(9):918-923.
[28] 周栩茹,王熙,田洁,等.黏附斑激酶在宫颈癌组织中表达及意义[J].昆明医科大学学报,2019,40(1):87-91. |
|
|
|