信号通路在胃癌转移中作用的研究进展

doi:10.16352/j.issn.1001-6325.2023.11.1707

摘要/Abstract

摘要： 细胞中不同的信号通路交互作用、互相调控形成一个动态的信号转导网络,参与肿瘤的发生发展,而胃癌的转移就是由各种信号通路调节影响的结果。肿瘤转移通常在临床上与较差的患者预后直接相关,因此深入研究影响胃癌转移的信号通路对晚期胃癌患者的治疗可提供帮助。

关键词: 胃癌, 转移, 转化生长因子β(TGFβ), 磷脂酰肌醇3激酶(PI3K), 信号通路

Abstract: The interaction and mutual regulation of different signaling pathways in cells form a dynamic signal transduction network, which is involved in the development of tumors, as the distant metastasis of gastric cancer is the result of regulation and influence of various signaling pathways. Cancer metastasis is often directly associated with poor prognosis, thus in-depth study of the signaling pathway affecting gastric cancer metastasis is essential strategy to optimize the treatment of advanced gastric cancer patients.

Key words: gastric cancer, metastasis, transforming growth factor-β(TGFβ), phosphatidylinositol 3-kinase(PI3K), signaling pathway

中图分类号:

R735.2

杨蛟洋, 舒格格, 李东宝, 周进. 信号通路在胃癌转移中作用的研究进展[J]. 基础医学与临床, 2023, 43(11): 1707-1712.

YANG Jiaoyang, SHU Gege, LI Dongbao, ZHOU Jin. Research progress of signaling pathways in gastric cancer metastasis[J]. Basic & Clinical Medicine, 2023, 43(11): 1707-1712.

参考文献 36

[1]	Song C,Zhou C. HOXA10 mediates epithelial-mesenchymal transition to promote gastric cancer metastasis partly via modulation of TGFB2/Smad/METTL3 signaling axis[J]. J Exp Clin Cancer Res, 2021, 401: 62.doi: 10.1186/s13046-021-01859-0.
[2]	You X, Wu J, Zhao X, et al. Fibroblastic galectin-1-fostered invasion and metastasis are mediated by TGF-β1-induced epithelial-mesenchymal transition in gastric cancer[J]. Aging (Albany NY), 2021, 1314: 18464-18481.
[3]	Zhang X, Zhang P, Shao M, et al. SALL4 activates TGF-β/SMAD signaling pathway to induce EMT and promote gastric cancer metastasis[J]. Cancer Manag Res, 2018, 10: 4459-4470.
[4]	Liu J, Dai X, Guo X, et al. Circ-OXCT1 suppresses gastric cancer EMT and metastasis by attenuating TGF-β pathway through the Circ-OXCT1/miR-136/SMAD4 axis[J]. Onco Targets Ther, 2020, 13: 3987-3998.
[5]	Li B, Xia Y, Lv J, et al. miR-151a-3p-rich small extracellular vesicles derived from gastric cancer accelerate liver metastasis via initiating a hepatic stemness-enhancing niche[J]. Oncogene, 2021, 4043: 6180-6194.
[6]	Lu J, Bang H, Kim SM, et al. Lymphatic metastasis-related TBL1XR1 enhances stemness and metastasis in gastric cancer stem-like cells by activating ERK1/2-SOX2 signaling[J]. Oncogene, 2021, 405: 922-936.
[7]	Kim BK, Cheong JH, Im JY, et al. PI3K/AKT/β-catenin signaling regulates vestigial-like 1 which predicts poor prognosis and enhances malignant phenotype in gastric cancer[J]. Cancers (Basel), 2019, 1112.doi: 10.3390/cancers11121923.
[8]	Du F, Feng W, Chen S, et al. Sex determining region Y-box 12 (SOX12) promotes gastric cancer metastasis by upregulating MMP7 and IGF1[J]. Cancer Lett, 2019, 452: 103-118.
[9]	Jiang L, Chen Y, Min G, et al. Bcl2-associated athanogene 4 promotes the invasion and metastasis of gastric cancer cells by activating the PI3K/AKT/NF-κB/ZEB1 axis[J]. Cancer Lett, 2021, 520: 409-421.
[10]	Xu E, Xia X, Jiang C, et al. GPER1 silencing suppres-ses the proliferation, migration, and invasion of gastric cancer cells by inhibiting PI3K/AKT-mediated EMT[J]. Front Cell Dev Biol, 2020, 8: 591239.doi: 10.3389/fcell.2022.841792.
[11]	张生军,常琦,刘敏丽. Livin通过Akt信号途径促进胃癌SGC7901细胞的上皮细胞间质转换[J]. 基础医学与临床, 2016, 365: 586-589.
[12]	Liu W, Gou H, Wang X, et al. TTPAL promotes gastric tumorigenesis by directly targeting NNMT to activate PI3K/AKT signaling[J]. Oncogene, 2021, 4049: 6666-6679.
[13]	Liang X, Qin C, Yu G, et al. Circular RNA circRAB31 acts as a miR-885-5psponge to suppress gastric cancer progressionvia the PTEN/PI3K/AKT pathway[J]. Mol Ther Oncolytics, 2021, 23: 501-514.
[14]	Ge Q, Hu Y, He J, et al. Zic1 suppresses gastric cancer metastasis by regulating Wnt/β-catenin signaling and epithelial-mesenchymal transition[J]. Faseb J, 2020, 342: 2161-2172.
[15]	Tian S, Peng P, Li J, et al. SERPINH1 regulates EMT and gastric cancer metastasis via the Wnt/β-catenin signaling pathway[J]. Aging (Albany NY), 2020, 124: 3574-3593.
[16]	Chi HC, Tsai CY, Wang CS, et al. DOCK6 promotes chemo-and radioresistance of gastric cancer by modulating WNT/β-catenin signaling and cancer stem cell traits[J]. Oncogene, 2020, 3937: 5933-5949.
[17]	Peng Y, Xu Y, Zhang X, et al. A novel protein AXIN1-295aa encoded by circAXIN1 activates the Wnt/β-catenin signaling pathway to promote gastric cancer progression[J]. Mol Cancer, 2021, 201: 158.doi: 10.1186/s12943-021-01457-w.
[18]	Yang XZ, Cheng TT, He QJ, et al. LINC01133 as ceRNA inhibits gastric cancer progression by sponging miR-106a-3p to regulate APC expression and the Wnt/β-catenin pathway[J]. Mol Cancer, 2018, 171: 126.doi: 10.1186/s12943-018-0874-1.
[19]	Gao Z, Long Y, Wu Y, et al. LncRNA LINC02253 activates KRT18/MAPK/ERK pathway by mediating N6-methyladenosine modification of KRT18 mRNA in gastric cancer[J]. Carcinogenesis, 2022, 435: 419-429.
[20]	Shi Y,Sun H. Down-regulation of lncRNA LINC00152 suppresses gastric cancer cell migration and invasion through inhibition of the ERK/MAPK signaling pathway[J]. Onco Targets Ther, 2020, 13: 2115-2124.
[21]	Sun YY, Zhang H, Ma RR, et al. Long non-coding RNA AK025387 promotes cell migration and invasion of gastric cancer[J]. Front Oncol, 2020, 10: 633.doi: 10.3389/fonc.2020.00633.
[22]	Wang X, Liang Q, Zhang L, et al. C8orf76 promotes gastric tumorigenicity and metastasis by directly inducing lncRNA DUSP5P1 and associates with patient outcomes[J]. Clin Cancer Res, 2019, 2510: 3128-3140.
[23]	Sun B,Zhong FJ. ELTD1 promotes gastric cancer cell proliferation, invasion and epithelial-mesenchymal transition through MAPK/ERK signaling by regulating CSK[J]. Int J Gen Med, 2021, 14: 4897-4911.
[24]	Zhang C, Zhao S, Tan Y, et al. The SKA3-DUSP2 axis promotes gastric cancer tumorigenesis and epithelial-mesenchymal transition by activating the MAPK/ERK pathway[J]. Front Pharmacol, 2022, 13: 777612.doi: 10.3389/fphar.2022.777612.
[25]	Doheny D, Manore SG, Wong GL, et al. Hedgehog signaling and truncated GLI1 in cancer[J]. Cells, 2020, 99.doi: 10.3390/cells9092114.
[26]	Xu QH, Xiao Y, Li XQ, et al. Resveratrol counteracts hypoxia-induced gastric cancer invasion and EMT through Hedgehog pathway suppression[J]. Anticancer Agents Med Chem, 2020, 209: 1105-1114.
[27]	Wu L, Wang S, Tang B, et al. Human telomerase reverse transcriptase (hTERT) synergistic with Sp1 upregulate Gli1 expression and increase gastric cancer invasion and metastasis[J]. J Mol Histol, 2021, 526: 1165-1175.
[28]	Sun DP, Tian YF, Lin CC, et al. A novel mechanism driving poor-prognostic gastric cancer: overexpression of the transcription factor Krüppel-like factor 16 promotes growth and metastasis of gastric cancer through regulating the Notch pathway[J]. Am J Cancer Res, 2021, 116: 2717-2735.
[29]	Huang B, Jin G, Qu C, et al. Elevated expression of NOTCH1 associates with lymph node metastasis of gastric cancer and knock-down of NOTCH1 attenuates tumor cell progression[J]. Med Sci Monit, 2019, 25: 9939-9948.
[30]	Liu Z, Li J, Ding Y, et al. USP49 mediates tumor progression and poor prognosis through a YAP1-dependent feedback loop in gastric cancer[J]. Oncogene, 2022, 4118: 2555-2570.
[31]	Liu H, Liu N, Zhao Y, et al. Oncogenic USP22 supports gastric cancer growth and metastasis by activating c-Myc/NAMPT/SIRT1-dependent FOXO1 and YAP signaling[J]. Aging (Albany NY), 2019, 1121: 9643-9660.
[32]	Gao Y, Li J, Xi H, et al. Stearoyl-CoA-desaturase-1 regulates gastric cancer stem-like properties and promotes tumour metastasis via Hippo/YAP pathway[J]. Br J Cancer, 2020, 12212: 1837-1847.
[33]	Zhou W, Xian Q, Wang Q, et al. m6A methyltransferase 3 promotes the proliferation and migration of gastric cancer cells through the m6A modification of YAP1[J]. J Oncol, 2021, 2021: 8875424.doi: 10.1155/2021/8875424.
[34]	Yao Y, Liu Z, Huang S, et al. The E3 ubiquitin ligase, FBXW5, promotes the migration and invasion of gastric cancer through the dysregulation of the Hippo pathway[J]. Cell Death Discov, 2022, 81: 79.doi: 10.1038/s41420-022-00868-y.
[35]	Yang Y, Zhang Q, Liang J, et al. STAM2 knockdown inhibits proliferation, migration, and invasion by affecting the JAK2/STAT3 signaling pathway in gastric cancer[J]. Acta Biochim Biophys Sin (Shanghai), 2021, 536: 697-706.
[36]	Wei KL, Chou JL, Chen YC, et al. Epigenetic silencing of STAT3-targeted miR-193a, by constitutive activation of JAK/STAT signaling, leads to tumor progression through overexpression of YWHAZ in gastric cancer[J]. Front Oncol, 2021, 11: 575667.doi: 10.3389/fonc.2021.575667.