食管鳞癌中STMN3高表达及其促癌作用机制

doi:10.3969/j.issn.1004-616x.2025.02.001

癌变·畸变·突变 ›› 2025, Vol. 37 ›› Issue (2): 89-95,104.doi: 10.3969/j.issn.1004-616x.2025.02.001

• 论著 • 下一篇

食管鳞癌中STMN3高表达及其促癌作用机制

郭婧, 谢观超, 王意浓, 蔡岩, 张钰, 王明荣, 郝佳洁

国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院, 分子肿瘤学全国重点实验室, 北京 100021

收稿日期:2025-01-05 修回日期:2025-03-04 出版日期:2025-03-30 发布日期:2025-04-11
通讯作者: 郝佳洁
作者简介:郭婧，E-mail:gj102066@163.com。
基金资助:
国家自然科学基金(81930077)；中国医学科学院医学与健康科技创新工程(2021-1-I2M-018)

High expression of STMN3 and its oncogenic mechanism in esophageal squamous cell carcinoma

GUO Jing, XIE Guanchao, WANG Yinong, CAI Yan, ZHANG Yu, WANG Mingrong, HAO Jiajie

State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China

Received:2025-01-05 Revised:2025-03-04 Online:2025-03-30 Published:2025-04-11

摘要/Abstract

摘要： 目的：分析STMN3在食管鳞癌中的表达情况，研究其对食管鳞癌细胞恶性表型的影响及相关调控机制。方法：利用癌症基因组图谱(TCGA)数据库分析STMN3 mRNA在不同肿瘤中的表达情况及其与患者临床病理指标之间的相关性，癌症细胞系百科全书(CCLE)数据库分析食管鳞癌细胞系中STMN3 mRNA的表达情况。采用Western blot法检测食管鳞癌细胞系中STMN3蛋白及其调控的下游蛋白的表达水平；分别采用RT-qPCR和Western blot法检测STMN3 siRNA转染在食管癌细胞系中的敲低效率；用细胞增殖、集落形成及细胞凋亡实验检测STMN3对食管鳞癌细胞恶性表型的影响。结果：与对照组比较，STMN3 mRNA在食管鳞癌及多种肿瘤组织中高表达，且高表达的食管鳞癌患者预后较差(P<0.05)。敲低STMN3可显著降低食管鳞癌细胞的增殖和集落形成能力(P<0.01)。Western blot结果显示，敲低STMN3后，表皮生长因子受体(EGFR)的蛋白表达水平，EGFR、核糖体蛋白S6、非受体酪氨酸激酶SRC的磷酸化水平均降低。结论：STMN3在食管鳞癌组织中高表达，且STMN3通过激活EGFR相关信号通路促进食管鳞癌细胞的增殖。

关键词: STMN3, 食管鳞癌, 细胞增殖, 细胞凋亡, 表皮生长因子受体

Abstract: OBJECTIVE：To investigate expression and mechanism of STMN3 in malignancy of esophageal squamous cell carcinoma (ESCC). METHODS：Expression of STMN3 in different tumors was analyzed in the TCGA database and its correlation with clinicopathological parameters was evaluated. CCLE database and Western blot were used to detect expression of STMN3 mRNA and protein levels in ESCC cell lines in vitro. Knockdown efficiency of STMN3 siRNA transfection in the cell lines was detected by RT-qPCR and Western blot，respectively. Effects of STMN3 on malignant phenotype of ESCC cells were detected by cell proliferation，colony formation，and cell apoptosis assays. The changes in the expression of proliferation-related proteins regulated by STMN3 were detected by Western blot. RESULTS：Compared with control group，STMN3 mRNA and protein were highly expressed in ESCC tissues and cell lines. STMN3 expression was associated with prognosis of patients，and those with high STMN3 expression had significantly worse prognosis (P<0.05). Knocking down STMN3 significantly inhibited the proliferation and colony formation of ESCC cells (P<0.01). In addition，the protein levels of EGFR and the phosphorylation levels of EGFR，S6，and SRC were significantly reduced. CONCLUSION：STMN3 was highly expressed in ESCC tissues，and STMN3 promoted the proliferation of ESCC cells by activating the EGFR-related signaling pathway.

Key words: STMN3, esophageal squamous cell carcinoma, cell proliferation, cell apoptosis, EGFR

中图分类号:

R735.1

郭婧, 谢观超, 王意浓, 蔡岩, 张钰, 王明荣, 郝佳洁. 食管鳞癌中STMN3高表达及其促癌作用机制[J]. 癌变·畸变·突变, 2025, 37(2): 89-95,104.

GUO Jing, XIE Guanchao, WANG Yinong, CAI Yan, ZHANG Yu, WANG Mingrong, HAO Jiajie. High expression of STMN3 and its oncogenic mechanism in esophageal squamous cell carcinoma[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2025, 37(2): 89-95,104.

参考文献

[1] HAN B F, ZHENG R S, ZENG H M, et al. Cancer incidence and mortality in China, 2022[J]. J Natl Cancer Cent, 2024, 4(1):47-53.
[2] LIANG T T, LU L, SONG X T, et al. Combination of microtubule targeting agents with other antineoplastics for cancer treatment[J]. Biochim Biophys Acta Rev Cancer, 2022, 1877(5):188777.
[3] ČERMÁK V, DOSTÁL V, JELÍNEK M, et al. Microtubule-targeting agents and their impact on cancer treatment[J]. Eur J Cell Biol, 2020, 99(4):151075.
[4] BELLETTI B, BALDASSARRE G. Stathmin:a protein with many tasks. New biomarker and potential target in cancer[J]. Expert Opin Ther Targets, 2011, 15(11):1249-1266.
[5] RONG B X, CAI X G, LIU H, et al. Stathmin-dependent molecular targeting therapy for malignant tumor:the latest 5 years' discoveries and developments[J]. J Transl Med, 2016, 14(1):279.
[6] JU W T, MA H L, ZHAO T C, et al. Stathmin guides personalized therapy in oral squamous cell carcinoma[J]. Cancer Sci, 2020, 111(4):1303-1313.
[7] ZARIN B, ESHRAGHI A, ZARIFI F, et al. A review on the role of tau and stathmin in gastric cancer metastasis[J]. Eur J Pharmacol, 2021, 908:174312.
[8] XIE Z, ZHEN T T, LIN Y, et al. The prognostic role of a phospho-Stathmin 1 signature in breast cancer treated with neoadjuvant chemotherapy[J]. Gland Surg, 2022, 11(11):1808-1816.
[9] ZHONG F J, SUN B, CAO M M, et al. STMN2 mediates nuclear translocation of Smad2/3 and enhances TGFβ signaling by destabilizing microtubules to promote epithelial-mesenchymal transition in hepatocellular carcinoma[J]. Cancer Lett, 2021, 506:128-141.
[10] ZHANG Y M, NI S L, HUANG B, et al. Overexpression of SCLIP promotes growth and motility in glioblastoma cells[J]. Cancer Biol Ther, 2015, 16(1):97-105.
[11] SINGER S, MALZ M, HERPEL E, et al. Coordinated expression of stathmin family members by far upstream sequence element-binding protein-1 increases motility in non-small cell lung cancer[J]. Cancer Res, 2009, 69(6):2234-2243.
[12] NAIR S, BORA-SINGHAL N, PERUMAL D, et al. Nicotine-mediated invasion and migration of non-small cell lung carcinoma cells by modulating STMN3 and GSPT1 genes in an ID1-dependent manner[J]. Mol Cancer, 2014, 13:173.
[13] XIE X M, BARTHOLOMEUSZ C, AHMED A A, et al. Bisphosphorylated PEA-15 sensitizes ovarian cancer cells to paclitaxel by impairing the microtubule-destabilizing effect of SCLIP[J]. Mol Cancer Ther, 2013, 12(6):1099-1111.
[14] LAWRENCE E J, CHATTERJEE S, ZANIC M. More is different:Reconstituting complexity in microtubule regulation[J]. J Biol Chem, 2023, 299(12):105398.
[15] PAIM L M G, LOPEZ-JAUREGUI A A, MCALEAR T S, et al. The spindle protein CKAP2 regulates microtubule dynamics and ensures faithful chromosome segregation[J]. Proc Natl Acad Sci USA, 2024, 121(9):e2318782121.
[16] LU Y, LIU C, XU Y F, et al. Stathmin destabilizing microtubule dynamics promotes malignant potential in cancer cells by epithelial-mesenchymal transition[J]. Hepatobiliary Pancreat Dis Int, 2014, 13(4):386-394.
[17] CAMPANACCI V, GIGANT B. The C-terminus of stathmin-like proteins governs the stability of their complexes with tubulin[J]. Biochem Biophys Res Commun, 2023, 682:244-249.
[18] LIPS E H, VAN EIJK R, DE GRAAF E J R, et al. Integrating chromosomal aberrations and gene expression profiles to dissect rectal tumorigenesis[J]. BMC Cancer, 2008, 8:314.
[19] KWAK Y, NAM S K, PARK Y, et al. Distinctive phenotypic and microenvironmental characteristics of neuroendocrine carcinoma and adenocarcinoma components in gastric mixed adenoneuroendocrine carcinoma[J]. Mod Pathol, 2024, 37(10):100568.
[20] SHEN C, YAN Y, YANG S B, et al. Construction and validation of a bladder cancer risk model based on autophagy-related genes[J]. Funct Integr Genomics, 2023, 23(1):46.
[21] WU X P, SOOMAN L, LENNARTSSON J, et al. Microtubule inhibition causes epidermal growth factor receptor inactivation in oesophageal cancer cells[J]. Int J Oncol, 2013, 42(1):297-304.
[22] ZARYOUH H, DE PAUW I, BAYSAL H, et al. Recent insights in the PI3K/Akt pathway as a promising therapeutic target in combination with EGFR-targeting agents to treat head and neck squamous cell carcinoma[J]. Med Res Rev, 2022, 42(1):112-155.
[23] YANG Y M, HONG P, XU W W, et al. Advances in targeted therapy for esophageal cancer[J]. Signal Transduct Target Ther, 2020, 5(1):229.
[24] WANG Y N, LIU C, CHEN H, et al. Clinical efficacy and identification of factors confer resistance to afatinib (tyrosine kinase inhibitor) in EGFR-overexpressing esophageal squamous cell carcinoma[J]. Signal Transduct Target Ther, 2024, 9(1):153.
[25] YI Y W, YOU K S, PARK J S, et al. Ribosomal protein S6:a potential therapeutic target against cancer-[J]. Int J Mol Sci, 2021, 23(1):48.
[26] ARTEMENKO M, ZHONG S S W, TO S K Y, et al. p70 S6 kinase as a therapeutic target in cancers:More than just an mTOR effector[J]. Cancer Lett, 2022, 535:215593.
[27] PANWAR V, SINGH A, BHATT M, et al. Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease[J]. Signal Transduct Target Ther, 2023, 8(1):375.
[28] PELAZ S G, TABERNERO A. Src:coordinating metabolism in cancer[J]. Oncogene, 2022, 41(45):4917-4928.
[29] POH A R, ERNST M. Functional roles of SRC signaling in pancreatic cancer:Recent insights provide novel therapeutic opportunities[J]. Oncogene, 2023, 42(22):1786-1801.
[30] CHEN Z W, OH D, DUBEY A K, et al. EGFR family and Src family kinase interactions:mechanics matters-[J]. Curr Opin Cell Biol, 2018, 51:97-102.
[31] ÁLVAREZ-VÁZQUEZ A, SAN-SEGUNDO L, CERVERÓ-GARCÍA P, et al. EGFR amplification and EGFRvIII predict and participate in TAT-Cx43266-283 antitumor response in preclinical glioblastoma models[J]. Neuro Oncol, 2024, 26(7):1230-1246.

食管鳞癌中STMN3高表达及其促癌作用机制

High expression of STMN3 and its oncogenic mechanism in esophageal squamous cell carcinoma

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