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GLI1 activation is a key mechanism of erlotinib resistance in human non‑small cell lung cancer

  • Authors:
    • Zhouhuan Dong
    • Yun Wang
    • Vivianne Ding
    • Xiang Yan
    • Yali Lv
    • Mei Zhong
    • Fengwei Zhu
    • Po Zhao
    • Charlotte He
    • Feng Ding
    • Huaiyin Shi
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China, Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94115, USA, Department of Medical Oncology, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China, Zhejiang Provincial Key Laboratory of Applied Enzymology and Precision Medicine Center, Jiaxing, Zhejiang 314006, P.R. China
    Copyright: © Dong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 76
    |
    Published online on: July 31, 2020
       https://doi.org/10.3892/ol.2020.11937
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Abstract

Lung cancer is the leading cause of cancer‑associated death worldwide. In recent years, the advancement of epidermal growth factor receptor‑tyrosine kinase inhibitor (EGFR‑TKI) targeted therapies has provided clinical benefits for lung cancer patients with EGFR mutations. The response to EGFR‑TKI varies in patients with lung cancer, and resistance typically develops during the course of the treatment. Therefore, understanding biomarkers which can predict resistance to EGFR‑TKI is important. Overexpression of GLI causes activation of the Hedgehog (Hh) signaling pathway and plays a critical role in oncogenesis in numerous types of cancer. In the present study, the role of GLI1 in erlotinib resistance was investigated. GLI1 mRNA and protein expression levels were determined using reverse transcription‑quantitative PCR and immunohistochemistry (IHC) in lung cancer cell lines and tumor specimens, respectively. GLI1 mRNA expression levels were found to be positively correlated with the IC50 of erlotinib in 15 non‑small cell lung cancer (NSCLC) cell lines. The downregulation of GLI1 using siRNA sensitized lung cancer cells to the erlotinib treatment, whereas the overexpression of GLI1 increased the survival of lung cancer cells in the presence of erlotinib, indicating that Hh/GLI activation may play a critical role in the development of TKI resistance in lung cancer. Combined treatment with erlotinib and a GLI1 inhibitor reduced the cell viability synergistically. A retrospective study of patients with NSCLC treated with erlotinib revealed that those with a high IHC score for GLI1 protein expression had a poorer prognosis. These results indicated that GLI1 is a key regulator for TKI sensitivity, and patients with lung cancer may benefit from the combined treatment of TKI and GLI1 inhibitor.
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View References

1 

Boloker G, Wang C and Zhang J: Updated statistics of lung and bronchus cancer in United States (2018). J Thorac Dis. 10:1158–1161. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI

3 

Duma N, Santana-Davila R and Molina JR: Non-small cell lung cancer: Epidemiology, screening, diagnosis, and treatment. Mayo Clin Proc. 94:1623–1640. 2019. View Article : Google Scholar : PubMed/NCBI

4 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2018. CA Cancer J Clin. 68:7–30. 2018. View Article : Google Scholar : PubMed/NCBI

5 

Cronin KA, Lake AJ, Scott S, Sherman RL, Noone AM, Howlader N, Henley SJ, Anderson RN, Firth AU, Ma J, et al: Annual report to the nation on the status of cancer, part I: National cancer statistics. Cancer. 124:2785–2800. 2018. View Article : Google Scholar : PubMed/NCBI

6 

Feng RM, Zong YN, Cao SM and Xu RH: Current cancer situation in China: Good or bad news from the 2018 global cancer statistics? Cancer Commun (Lond). 39:222019. View Article : Google Scholar : PubMed/NCBI

7 

da Cunha Santos G, Shepherd FA and Tsao MS: EGFR mutations and lung cancer. Annu Rev Pathol. 6:49–69. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, et al: EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science. 304:1497–1500. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Selvaggi G, Novello S, Torri V, Leonardo E, De Giuli P, Borasio P, Mossetti C, Ardissone F, Lausi P and Scagliotti GV: Epidermal growth factor receptor overexpression correlates with a poor prognosis in completely resected non-small-cell lung cancer. Ann Oncol. 15:28–32. 2004. View Article : Google Scholar : PubMed/NCBI

10 

Sharma SV, Bell DW, Settleman J and Haber DA: Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer. 7:169–181. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, Zakowski MF, Kris MG and Varmus H: Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med. 2:e732005. View Article : Google Scholar : PubMed/NCBI

12 

Kobayashi S, Boggon TJ, Dayaram T, Jänne PA, Kocher O, Meyerson M, Johnson BE, Eck MJ, Tenen DG and Halmos B: EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med. 352:786–792. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Gazdar AF: Activating and resistance mutations of EGFR in non-small-cell lung cancer: Role in clinical response to EGFR tyrosine kinase inhibitors. Oncogene. 28 (Suppl 1):S24–S31. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Pao W, Wang TY, Riely GJ, Miller VA, Pan Q, Ladanyi M, Zakowski MF, Heelan RT, Kris MG and Varmus HE: KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med. 2:e172005. View Article : Google Scholar : PubMed/NCBI

15 

Takezawa K, Pirazzoli V, Arcila ME, Nebhan CA, Song X, de Stanchina E, Ohashi K, Janjigian YY, Spitzler PJ, Melnick MA, et al: HER2 amplification: A potential mechanism of acquired resistance to EGFR inhibition in EGFR-mutant lung cancers that lack the second-site EGFRT790M mutation. Cancer Discov. 2:922–933. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO, Lindeman N, Gale CM, Zhao X, Christensen J, et al: MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. 316:1039–1043. 2007. View Article : Google Scholar : PubMed/NCBI

17 

Massarelli E, Varella-Garcia M, Tang X, Xavier AC, Ozburn NC, Liu DD, Bekele BN, Herbst RS and Wistuba II: KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. Clin Cancer Res. 13:2890–2896. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Dragnev KH, Ma T, Cyrus J, Galimberti F, Memoli V, Busch AM, Tsongalis GJ, Seltzer M, Johnstone D, Erkmen CP, et al: Bexarotene plus erlotinib suppress lung carcinogenesis independent of KRAS mutations in two clinical trials and transgenic models. Cancer Prev Res (Phila). 4:818–828. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Linardou H, Dahabreh IJ, Kanaloupiti D, Siannis F, Bafaloukos D, Kosmidis P, Papadimitriou CA and Murray S: Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: A systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer. Lancet Oncol. 9:962–972. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Wu SG and Shih JY: Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer. Mol Cancer. 17:382018. View Article : Google Scholar : PubMed/NCBI

21 

Merchant AA and Matsui W: Targeting hedgehog-a cancer stem cell pathway. Clin Cancer Res. 16:3130–3140. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Velcheti V and Govindan R: Hedgehog signaling pathway and lung cancer. J Thorac Oncol. 2:7–10. 2007. View Article : Google Scholar : PubMed/NCBI

23 

Amakye D, Jagani Z and Dorsch M: Unraveling the therapeutic potential of the hedgehog pathway in cancer. Nat Med. 19:1410–1422. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Yuan Z, Goetz JA, Singh S, Ogden SK, Petty WJ, Black CC, Memoli VA, Dmitrovsky E and Robbins DJ: Frequent requirement of hedgehog signaling in non-small cell lung carcinoma. Oncogene. 26:1046–1055. 2007. View Article : Google Scholar : PubMed/NCBI

25 

Giroux-Leprieur E, Costantini A, Ding VW and He B: Hedgehog signaling in lung cancer: From oncogenesis to cancer treatment resistance. Int J Mol Sci. 19:28352018. View Article : Google Scholar

26 

Niyaz M, Khan MS and Mudassar S: Hedgehog signaling: An achilles' heel in cancer. Transl Oncol. 12:1334–1344. 2019. View Article : Google Scholar : PubMed/NCBI

27 

Sabol M, Trnski D, Musani V, Ozretić P and Levanat S: Role of GLI transcription factors in pathogenesis and their potential as new therapeutic targets. Int J Mol Sci. 19:25622018. View Article : Google Scholar

28 

Ruiz i Altaba A: Gli proteins encode context-dependent positive and negative functions: Implications for development and disease. Development. 126:3205–3216. 1999.PubMed/NCBI

29 

Hui CC and Angers S: Gli proteins in development and disease. Annu Rev Cell Dev Biol. 27:513–537. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Niewiadomski P, Niedziółka SM, Markiewicz Ł, Uśpieński T, Baran B and Chojnowska K: Gli proteins: Regulation in development and cancer. Cells. 8:1472019. View Article : Google Scholar

31 

Sasaki H, Nishizaki Y, Hui C, Nakafuku M and Kondoh H: Regulation of Gli2 and Gli3 activities by an amino-terminal repression domain: Implication of Gli2 and Gli3 as primary mediators of Shh signaling. Development. 126:3915–3924. 1999.PubMed/NCBI

32 

Yang L, Xie G, Fan Q and Xie J: Activation of the hedgehog-signaling pathway in human cancer and the clinical implications. Oncogene. 29:469–481. 2010. View Article : Google Scholar : PubMed/NCBI

33 

Sekulic A, Migden MR, Oro AE, Dirix L, Lewis KD, Hainsworth JD, Solomon JA, Yoo S, Arron ST, Friedlander PA, et al: Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 366:2171–2179. 2012. View Article : Google Scholar : PubMed/NCBI

34 

Basset-Séguin N, Hauschild A, Kunstfeld R, Grob J, Dréno B, Mortier L, Ascierto PA, Licitra L, Dutriaux C, Thomas L, et al: Vismodegib in patients with advanced basal cell carcinoma: Primary analysis of STEVIE, an international, open-label trial. Eur J Cancer. 86:334–348. 2017. View Article : Google Scholar : PubMed/NCBI

35 

Lear JT, Migden MR, Lewis KD, Chang ALS, Guminski A, Gutzmer R, Dirix L, Combemale P, Stratigos A, Plummer R, et al: Long-term efficacy and safety of sonidegib in patients with locally advanced and metastatic basal cell carcinoma: 30-month analysis of the randomized phase 2 BOLT study. J Eur Acad Dermatol Venereol. 32:372–381. 2018. View Article : Google Scholar : PubMed/NCBI

36 

Rodon J, Tawbi HA, Thomas AL, Stoller RG, Turtschi CP, Baselga J, Sarantopoulos J, Mahalingam D, Shou Y, Moles MA, et al: A phase I, multicenter, open-label, first-in-human, dose-escalation study of the oral smoothened inhibitor Sonidegib (LDE225) in patients with advanced solid tumors. Clin Cancer Res. 20:1900–1909. 2014. View Article : Google Scholar : PubMed/NCBI

37 

Kieran MW, Chisholm J, Casanova M, Brandes AA, Aerts I, Bouffet E, Bailey S, Leary S, MacDonald TJ, Mechinaud F, et al: Phase I study of oral sonidegib (LDE225) in pediatric brain and solid tumors and a phase II study in children and adults with relapsed medulloblastoma. Neuro Oncol. 19:1542–1552. 2017. View Article : Google Scholar : PubMed/NCBI

38 

Minami H, Ando Y, Ma BB, Hsiang Lee J, Momota H, Fujiwara Y, Li L, Fukino K, Ito K, Tajima T, et al: Phase I, multicenter, open-label, dose-escalation study of sonidegib in Asian patients with advanced solid tumors. Cancer Sci. 107:1477–1483. 2016. View Article : Google Scholar : PubMed/NCBI

39 

Ko AH, LoConte N, Tempero MA, Walker EJ, Kate Kelley R, Lewis S, Chang WC, Kantoff E, Vannier MW, Catenacci DV, et al: A Phase I study of FOLFIRINOX plus IPI-926, a hedgehog pathway inhibitor, for advanced pancreatic adenocarcinoma. Pancreas. 45:370–375. 2016. View Article : Google Scholar : PubMed/NCBI

40 

Jimeno A, Weiss GJ, Miller WH Jr, Gettinger S, Eigl BJ, Chang AL, Dunbar J, Devens S, Faia K, Skliris G, et al: Phase I study of the hedgehog pathway inhibitor IPI-926 in adult patients with solid tumors. Clin Cancer Res. 19:2766–2774. 2013. View Article : Google Scholar : PubMed/NCBI

41 

Lauth M and Toftgård R: Non-canonical activation of GLI transcription factors: Implications for targeted anti-cancer therapy. Cell Cycle. 6:2458–2463. 2007. View Article : Google Scholar : PubMed/NCBI

42 

Mimeault M and Batra SK: Frequent deregulations in the hedgehog signaling network and cross-talks with the epidermal growth factor receptor pathway involved in cancer progression and targeted therapies. Pharmacol Rev. 62:497–524. 2010. View Article : Google Scholar : PubMed/NCBI

43 

Ou SI and Shirai K: Anaplastic lymphoma kinase (ALK) signaling in lung cancer. Adv Exp Med Biol. 893:179–187. 2016. View Article : Google Scholar : PubMed/NCBI

44 

Garrido-Castro AC and Felip E: HER2 driven non-small cell lung cancer (NSCLC): Potential therapeutic approaches. Transl Lung Cancer Res. 2:122–127. 2013.PubMed/NCBI

45 

Benvenuto M, Masuelli L, De Smaele E, Fantini M, Mattera R, Cucchi D, Bonanno E, Di Stefano E, Frajese GV, Orlandi A, et al: In vitro and in vivo inhibition of breast cancer cell growth by targeting the Hedgehog/GLI pathway with SMO (GDC-0449) or GLI (GANT-61) inhibitors. Oncotarget. 7:9250–9270. 2016. View Article : Google Scholar : PubMed/NCBI

46 

Srivastava RK, Kaylani SZ, Edrees N, Li C, Talwelkar SS, Xu J, Palle K, Pressey JG and Athar M: GLI inhibitor GANT-61 diminishes embryonal and alveolar rhabdomyosarcoma growth by inhibiting Shh/AKT-mTOR axis. Oncotarget. 5:12151–12165. 2014. View Article : Google Scholar : PubMed/NCBI

47 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

48 

Ishikawa M, Sonobe M, Imamura N, Sowa T, Shikuma K and Date H: Expression of the GLI family genes is associated with tumor progression in advanced lung adenocarcinoma. World J Surg Oncol. 12:2532014. View Article : Google Scholar : PubMed/NCBI

49 

Tate JG, Bamford S, Jubb HC, Sondka Z, Beare DM, Bindal N, Boutselakis H, Cole CG, Creatore C, Dawson E, et al: COSMIC: The catalogue of somatic mutations in cancer. Nucleic Acids Res. 47:D941–D947. 2019. View Article : Google Scholar : PubMed/NCBI

50 

Forbes SA, Tang G, Bindal N, Bamford S, Dawson E, Cole C, Kok CY, Jia M, Ewing R, Menzies A, et al: COSMIC (the Catalogue of Somatic Mutations in Cancer): A resource to investigate acquired mutations in human cancer. Nucleic Acids Res. 38:D652–D657. 2010. View Article : Google Scholar : PubMed/NCBI

51 

Ramos AH, Dutt A, Mermel C, Perner S, Cho J, Lafargue CJ, Johnson LA, Stiedl AC, Tanaka KE, Bass AJ, et al: Amplification of chromosomal segment 4q12 in non-small cell lung cancer. Cancer Biol Ther. 8:2042–2050. 2009. View Article : Google Scholar : PubMed/NCBI

52 

Mo ML, Chen Z, Zhou HM, Li H, Hirata T, Jablons DM and He B: Detection of E2A-PBX1 fusion transcripts in human non-small-cell lung cancer. J Exp Clin Cancer Res. 32:292013. View Article : Google Scholar : PubMed/NCBI

53 

Bean J, Brennan C, Shih JY, Riely G, Viale A, Wang L, Chitale D, Motoi N, Szoke J, Broderick S, et al: MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci USA. 104:20932–20937. 2007. View Article : Google Scholar : PubMed/NCBI

54 

Minakata K, Takahashi F, Nara T, Hashimoto M, Tajima K, Murakami A, Nurwidya F, Yae S, Koizumi F, Moriyama H, et al: Hypoxia induces gefitinib resistance in non-small-cell lung cancer with both mutant and wild-type epidermal growth factor receptors. Cancer Sci. 103:1946–1954. 2012. View Article : Google Scholar : PubMed/NCBI

55 

Cortes JR, Ambesi-Impiombato A, Couronné L, Quinn SA, Kim CS, da Silva Almeida AC, West Z, Belver L, Martin MS, Scourzic L, et al: RHOA G17V induces T follicular helper cell specification and promotes lymphomagenesis. Cancer Cell. 33:259–273.e7. 2018. View Article : Google Scholar : PubMed/NCBI

56 

Pratilas CA, Hanrahan AJ, Halilovic E, Persaud Y, Soh J, Chitale D, Shigematsu H, Yamamoto H, Sawai A, Janakiraman M, et al: Genetic predictors of MEK dependence in non-small cell lung cancer. Cancer Res. 68:9375–9383. 2008. View Article : Google Scholar : PubMed/NCBI

57 

Landrum MJ, Lee JM, Riley GR, Jang W, Rubinstein WS, Church DM and Maglott DR: ClinVar: Public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res. 42:D980–D985. 2014. View Article : Google Scholar : PubMed/NCBI

58 

Bosco-Clément G, Zhang F, Chen Z, Zhou HM, Li H, Mikami I, Hirata T, Yagui-Beltran A, Lui N, Do HT, et al: Targeting Gli transcription activation by small molecule suppresses tumor growth. Oncogene. 33:2087–2097. 2014. View Article : Google Scholar : PubMed/NCBI

59 

Gialmanidis IP, Bravou V, Amanetopoulou SG, Varakis J, Kourea H and Papadaki H: Overexpression of hedgehog pathway molecules and FOXM1 in non-small cell lung carcinomas. Lung Cancer. 66:64–74. 2009. View Article : Google Scholar : PubMed/NCBI

60 

Bora-Singhal N, Perumal D, Nguyen J and Chellappan S: Gli1-mediated regulation of Sox2 facilitates self-renewal of stem-like cells and confers resistance to EGFR inhibitors in non-small cell lung cancer. Neoplasia. 17:538–551. 2015. View Article : Google Scholar : PubMed/NCBI

61 

Armas-López L, Piña-Sánchez P, Arrieta O, de Alba EG, Ortiz-Quintero B, Santillán-Doherty P, Christiani DC, Zúñiga J and Ávila-Moreno F: Epigenomic study identifies a novel mesenchyme homeobox2-GLI1 transcription axis involved in cancer drug resistance, overall survival and therapy prognosis in lung cancer patients. Oncotarget. 8:67056–67081. 2017. View Article : Google Scholar : PubMed/NCBI

62 

Dimou A, Bamias A, Gogas H and Syrigos K: Inhibition of the hedgehog pathway in lung cancer. Lung Cancer. 133:56–61. 2019. View Article : Google Scholar : PubMed/NCBI

63 

Nguyen KS, Kobayashi S and Costa DB: Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancers dependent on the epidermal growth factor receptor pathway. Clin Lung Cancer. 10:281–289. 2009. View Article : Google Scholar : PubMed/NCBI

64 

Sequist LV, Waltman BA, Dias-Santagata D, Digumarthy S, Turke AB, Fidias P, Bergethon K, Shaw AT, Gettinger S, Cosper AK, et al: Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med. 3:75ra262011. View Article : Google Scholar : PubMed/NCBI

65 

Cooke DT, Nguyen DV, Yang Y, Chen SL, Yu C and Calhoun RF: Survival comparison of adenosquamous, squamous cell, and adenocarcinoma of the lung after lobectomy. Ann Thorac Surg. 90:943–948. 2010. View Article : Google Scholar : PubMed/NCBI

66 

Kawase A, Yoshida J, Ishii G, Nakao M, Aokage K, Hishida T, Nishimura M and Nagai K: Differences between squamous cell carcinoma and adenocarcinoma of the lung: Are adenocarcinoma and squamous cell carcinoma prognostically equal? Jpn J Clin Oncol. 42:189–195. 2012. View Article : Google Scholar : PubMed/NCBI

67 

Bai XY, Zhang XC, Yang SQ, An SJ, Chen ZH, Su J, Xie Z, Gou LY and Wu YL: Blockade of hedgehog signaling synergistically increases sensitivity to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer cell lines. PLoS One. 11:e01493702016. View Article : Google Scholar : PubMed/NCBI

68 

Jin S, He J, Li J, Guo R, Shu Y and Liu P: MiR-873 inhibition enhances gefitinib resistance in non-small cell lung cancer cells by targeting glioma-associated oncogene homolog 1. Thorac Cancer. 9:1262–1270. 2018. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Dong Z, Wang Y, Ding V, Yan X, Lv Y, Zhong M, Zhu F, Zhao P, He C, Ding F, Ding F, et al: GLI1 activation is a key mechanism of erlotinib resistance in human non‑small cell lung cancer. Oncol Lett 20: 76, 2020.
APA
Dong, Z., Wang, Y., Ding, V., Yan, X., Lv, Y., Zhong, M. ... Shi, H. (2020). GLI1 activation is a key mechanism of erlotinib resistance in human non‑small cell lung cancer. Oncology Letters, 20, 76. https://doi.org/10.3892/ol.2020.11937
MLA
Dong, Z., Wang, Y., Ding, V., Yan, X., Lv, Y., Zhong, M., Zhu, F., Zhao, P., He, C., Ding, F., Shi, H."GLI1 activation is a key mechanism of erlotinib resistance in human non‑small cell lung cancer". Oncology Letters 20.4 (2020): 76.
Chicago
Dong, Z., Wang, Y., Ding, V., Yan, X., Lv, Y., Zhong, M., Zhu, F., Zhao, P., He, C., Ding, F., Shi, H."GLI1 activation is a key mechanism of erlotinib resistance in human non‑small cell lung cancer". Oncology Letters 20, no. 4 (2020): 76. https://doi.org/10.3892/ol.2020.11937
Copy and paste a formatted citation
x
Spandidos Publications style
Dong Z, Wang Y, Ding V, Yan X, Lv Y, Zhong M, Zhu F, Zhao P, He C, Ding F, Ding F, et al: GLI1 activation is a key mechanism of erlotinib resistance in human non‑small cell lung cancer. Oncol Lett 20: 76, 2020.
APA
Dong, Z., Wang, Y., Ding, V., Yan, X., Lv, Y., Zhong, M. ... Shi, H. (2020). GLI1 activation is a key mechanism of erlotinib resistance in human non‑small cell lung cancer. Oncology Letters, 20, 76. https://doi.org/10.3892/ol.2020.11937
MLA
Dong, Z., Wang, Y., Ding, V., Yan, X., Lv, Y., Zhong, M., Zhu, F., Zhao, P., He, C., Ding, F., Shi, H."GLI1 activation is a key mechanism of erlotinib resistance in human non‑small cell lung cancer". Oncology Letters 20.4 (2020): 76.
Chicago
Dong, Z., Wang, Y., Ding, V., Yan, X., Lv, Y., Zhong, M., Zhu, F., Zhao, P., He, C., Ding, F., Shi, H."GLI1 activation is a key mechanism of erlotinib resistance in human non‑small cell lung cancer". Oncology Letters 20, no. 4 (2020): 76. https://doi.org/10.3892/ol.2020.11937
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