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上皮-间充质转化影响肿瘤放疗敏感性研究进展
李家慧1,2, 柏玉举1,2
1遵义医科大学,遵义 563000; 2遵义医科大学第二附属医院胸部肿瘤科,遵义 563000
Advances in studies on the effect of epithelial-mesenchymal transformation on radiotherapy sensitivity of tumors
Li Jiahui1,2, Bai Yuju1,2
1Zunyi Medical University, Zunyi 563000, China; 2Department of Thoracic Oncology, the Second Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China
Abstract：Radiotherapy is one of the most important methods in the treatment of malignant tumors. However, the decrease of radiosensitivity of tumor cells is the main reason affecting the efficacy of radiotherapy. Epithelial-mesenchymal transition (EMT) is a complex biological process that confers several characteristics necessary for the progression of malignant tumors, such as tumor initiation, aggressiveness, transmissibility, and tolerance to chemotherapy and radiotherapy. In addition, EMT can also be induced by radiation, which endows tumor cells with radiation resistance. Previous studies have shown that inhibition of EMT could enhance the radiosensitivity of tumor cells, but the overall understanding of the molecular mechanisms, key targets and pathways involved are still lacking. In this article, recent studies on the role of EMT in tumor radiation therapy were reviewed, focusing on the signaling pathway, EMT-induced transcription factors, aiming to deepen the understanding of the effect of EMT on the sensitivity of radiotherapy and provide ideas for improving the clinical therapeutic effect of radiotherapy.
Li Jiahui,Bai Yuju. Advances in studies on the effect of epithelial-mesenchymal transformation on radiotherapy sensitivity of tumors[J]. Chinese Journal of Radiation Oncology, 2023, 32(4): 384-387.
[1] Pastushenko I, Brisebarre A, Sifrim A, et al.Identification of the tumour transition states occurring during EMT[J]. Nature, 2018,556(7702):463-468. DOI: 10.1038/s41586- 018-0040-3. [2] Zhang N, Ng AS, Cai S, et al.Novel therapeutic strategies: targeting epithelial-mesenchymal transition in colorectal cancer[J]. Lancet Oncol, 2021,22(8):e358-e368. DOI: 10. 1016/S1470-2045(21)00343-0. [3] Pastushenko I, Blanpain C.EMT transition states during tumor progression and metastasis[J]. Trends Cell Biol, 2019,29(3):212-226. DOI: 10.1016/j.tcb.2018.12.001. [4] Chen Y, Li WW, Peng P, et al.mTORC1 inhibitor RAD001 (everolimus) enhances non-small cell lung cancer cell radiosensitivity in vitro via suppressing epithelial- mesenchymal transition[J]. Acta Pharmacol Sin, 2019,40(8):1085-1094. DOI: 10.1038/s41401- 019-0215-y. [5] Dongre A, Weinberg RA.New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer[J]. Nat Rev Mol Cell Biol, 2019, 20(2):69-84. DOI: 10.1038/s41580-018-0080-4. [6] Peinado H, Olmeda D, Cano A.Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype?[J]. Nat Rev Cancer, 2007,7(6):415-428. DOI: 10.1038/nrc2131. [7] Bakir B, Chiarella AM, Pitarresi JR, et al.EMT, MET, plasticity, and tumor metastasis[J]. Trends Cell Biol, 2020,30(10):764-776. DOI: 10.1016/j.tcb.2020.07.003. [8] Lambert AW, Pattabiraman DR, Weinberg RA.Emerging biological principles of metastasis[J]. Cell, 2017,168(4):670-691. DOI: 10.1016/j.cell.2016.11.037. [9] Colton M, Cheadle EJ, Honeychurch J, et al.Reprogramming the tumour microenvironment by radiotherapy: implications for radiotherapy and immunotherapy combinations[J]. Radiat Oncol, 2020,15(1):254. DOI: 10.1186/s13014-020-01678-1. [10] Buckley AM, Lynam-Lennon N, O'Neill H, et al. Targeting hallmarks of cancer to enhance radiosensitivity in gastrointestinal cancers[J]. Nat Rev Gastroenterol Hepatol, 2020,17(5):298-313. DOI: 10.1038/s41575- 019-0247-2. [11] Xu YK, Wu GZ, Zhang JY, et al.TRIM33 overexpression inhibits the progression of clear cell renal cell carcinoma in vivo and in vitro[J]. Biomed Res Int, 2020,2020:8409239. DOI: 10.1155/2020/8409239. [12] Baumann M, Krause M, Hill R.Exploring the role of cancer stem cells in radioresistance[J]. Nat Rev Cancer, 2008,8(7):545-554. DOI: 10.1038/nrc2419. [13] Mani SA, Guo W, Liao MJ, et al.The epithelial-mesenchymal transition generates cells with properties of stem cells[J]. Cell, 2008,133(4):704-715. DOI: 10.1016/j.cell.2008.03.027. [14] He YL, Mingyan E, Wang CB, et al.CircVRK1 regulates tumor progression and radioresistance in esophageal squamous cell carcinoma by regulating miR-624-3p/PTEN/PI3K/AKT signaling pathway[J]. Int J Biol Macromol, 2019,125:116-123. DOI: 10.1016/j.ijbiomac. 2018.11.273. [15] Wang CQ, Zhang RZ, Wang X, et al.Silencing of KIF3B suppresses breast cancer progression by regulating EMT and Wnt/β-catenin signaling[J]. Front Oncol, 2020,10:597464. DOI: 10.3389/fonc.2020.597464. [16] Zhang JH, Si J, Gan L, et al.Inhibition of Wnt signalling pathway by XAV939 enhances radiosensitivity in human cervical cancer HeLa cells[J]. Artif Cells Nanomed Biotechnol, 2020,48(1):479-487. DOI: 10.1080/216914 01.2020.1716779. [17] Han PB, Ji XJ, Zhang M, et al.Upregulation of lncRNA LINC00473 promotes radioresistance of HNSCC cells through activating Wnt/β-catenin signaling pathway[J]. Eur Rev Med Pharmacol Sci, 2018,22(21):7305-7313. DOI: 10.26355/eurrev_201811_16267. [18] Lee SH, Kim O, Kim HJ, et al.Epigenetic regulation of TGF-β-induced EMT by JMJD3/KDM6B histone H3K27 demethylase[J]. Oncogenesis, 2021,10(2):17. DOI: 10.1038/s41389-021-00307-0. [19] Konge J, Leteurtre F, Goislard M, et al.Breast cancer stem cell-like cells generated during TGFβ-induced EMT are radioresistant[J]. Oncotarget, 2018,9(34):23519-23531. DOI: 10.18632/oncotarget.25240. [20] Yang T, Huang TH, Zhang DD, et al.TGF-β receptor inhibitor LY2109761 enhances the radiosensitivity of gastric cancer by inactivating the TGF-β/SMAD4 signaling pathway[J]. Aging (Albany NY), 2019,11(20):8892-8910. DOI: 10.18632/aging.102329. [21] Ahmed MM, Alcock RA, Chendil D, et al.Restoration of transforming growth factor-beta signaling enhances radiosensitivity by altering the Bcl-2/Bax ratio in the p53 mutant pancreatic cancer cell line MIA PaCa-2[J]. J Biol Chem, 2002,277(3):2234-2246. DOI: 10.1074/jbc.M110 168200. [22] Zhou Y, Shurin GV, Zhong H, et al.Schwann cells augment cell spreading and metastasis of lung cancer[J]. Cancer Res, 2018,78(20):5927-5939. DOI: 10.1158/0008-5472.CAN-18-1702. [23] Wu DP, Zhou Y, Hou LX, et al.Cx43 deficiency confers EMT-mediated tamoxifen resistance to breast cancer via c-Src/PI3K/Akt pathway[J]. Int J Biol Sci, 2021,17(10):2380-2398. DOI: 10.7150/ijbs.55453. [24] Zou NY, Zhang XY, Li SG, et al.Elevated HNF1A expression promotes radiation-resistance via driving PI3K/AKT signaling pathway in esophageal squamous cell carcinoma cells[J]. J Cancer, 2021,12(16):5013-5024. DOI: 10.7150/jca.58023. [25] Feng YL, Chen DQ, Vaziri ND, et al.Small molecule inhibitors of epithelial-mesenchymal transition for the treatment of cancer and fibrosis[J]. Med Res Rev, 2020,40(1):54-78. DOI: 10.1002/med.21596. [26] Zhou JS, Jain S, Azad AK, et al.Notch and TGFβ form a positive regulatory loop and regulate EMT in epithelial ovarian cancer cells[J]. Cell Signal, 2016,28(8):838-849. DOI: 10.1016/j.cellsig.2016.03.016. [27] Vermezovic J, Adamowicz M, Santarpia L, et al.Notch is a direct negative regulator of the DNA-damage response[J]. Nat Struct Mol Biol, 2015,22(5):417-424. DOI: 10.1038/nsmb.3013. [28] Zhang PJ, Wei YK, Wang L, et al.ATM-mediated stabilization of ZEB1 promotes DNA damage response and radioresistance through CHK1[J]. Nat Cell Biol, 2014,16(9):864-875. DOI: 10.1038/ncb3013. [29] Qiu ML, Chen DY, Shen CY, et al.Sex-determining region Y-box protein 3 induces epithelial-mesenchymal transition in osteosarcoma cells via transcriptional activation of Snail1[J]. J Exp Clin Cancer Res, 2017,36(1):46. DOI: 10.1186/s13046-017-0515-3. [30] Zhu Y, Wang C, Becker SA, et al.miR-145 antagonizes SNAI1-mediated stemness and radiation resistance in colorectal cancer[J]. Mol Ther, 2018,26(3):744-754. DOI: 10.1016/j.ymthe.2017.12.023. [31] Zhang KJ, Jiao XL, Liu XY, et al.Knockdown of snail sensitizes pancreatic cancer cells to chemotherapeutic agents and irradiation[J]. Int J Mol Sci, 2010,11(12):4891-4892. DOI: 10.3390/ijms11124891. [32] Jiang FF, Zhou LJ, Wei CB, et al.Slug inhibition increases radiosensitivity of oral squamous cell carcinoma cells by upregulating PUMA[J]. Int J Oncol, 2016,49(2):709-719. DOI: 10.3892/ijo.2016.3570. [33] Zhu QQ, Ma C, Wang Q, et al.The role of TWIST1 in epithelial-mesenchymal transition and cancers[J]. Tumour Biol, 2016,37(1):185-197. DOI: 10.1007/s1327 7-015-4450-7. [34] Ha J, Lee S, Park J, et al.Identification of a novel inhibitor of liver cancer cell invasion and proliferation through regulation of Akt and Twist1[J]. Sci Rep, 2021,11(1):16765. DOI: 10.1038/s41598-021-95933-4. [35] Yeeravalli R, Kaushik K, Das A.TWIST1-mediated transcriptional activation of PDGFRβ in breast cancer stem cells promotes tumorigenesis and metastasis[J]. Biochim Biophys Acta Mol Basis Dis, 2021,1867(7):166141. DOI: 10.1016/j.bbadis.2021.166141. [36] Chen SC, Liao TT, Yang MH.Emerging roles of epithelial-mesenchymal transition in hematological malignancies[J]. J Biomed Sci, 2018,25(1):37. DOI: 10. 1186/s12929-018-0440-6. [37] Seo SK, Kim JH, Choi HN, et al.Knockdown of TWIST1 enhances arsenic trioxide- and ionizing radiation-induced cell death in lung cancer cells by promoting mitochondrial dysfunction[J]. Biochem Biophys Res Commun, 2014,449(4):490-495. DOI: 10.1016/j.bbrc. 2014.05.030.
2023, Vol. 32 
