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Article

ERBB4 promotes the proliferation of gastric cancer cells via the PI3K/Akt signaling pathway

  • Authors:
    • Ji Xu
    • Lijie Gong
    • Zhenyuan Qian
    • Guangyuan Song
    • Jinming Liu
  • View Affiliations / Copyright

    Affiliations: Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, P.R. China, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China
  • Pages: 2892-2898
    |
    Published online on: March 30, 2018
       https://doi.org/10.3892/or.2018.6343
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Abstract

ERBB4 is one of the members of the epidermal growth factor receptor (EGFR) family. ERBB4 is a large transmembrane glycoprotein and has tyrosine kinase activity. Once combined with epidermal growth factor (EGF), ERBB4 can activate the related genes in the nucleus, thus promoting cell division and proliferation. In the present study, we investigated the effect of ERBB4 in the proliferation of gastric cancer cells. We found that high ERBB4 levels were closely related to the poor prognosis of gastric cancer patients. Furthermore, ERBB4 was highly expressed in gastric cancer cell lines when compared to the normal stomach cell line, GES. Clinical samples provided the same results. Two gastric cancer cell lines, SGC‑7901 and MNK‑45 were used to study the underlying mechanism of ERBB4 in the promotion of cell proliferation in gastric cancer cells both in vitro and in vivo. It was observed that after the expression of ERBB4 was suppressed, the proliferation of gastric cancer cells was markedly inhibited both in vitro and in vivo. Moreover, treatment with lentiviral vector siRNA‑ERBB4 (Lv‑siRNA‑ERBB4) or the ERBB4 inhibitor AST‑1306, markedly inhibited gastric cancer cell proliferation. Further experiments revealed that inhibition of the expression of ERBB4 could inhibit the activation of the PI3K/Akt signaling pathway. In addition, the use of the PI3K/Akt signaling pathway inhibitor LY294002 demonstrated the aforementioned results. Therefore, we believe that ERBB4 regulates cell proliferation mainly through the PI3K signaling pathway. Finally, nude mice xenografted with gastric cancer cells with low expression of ERBB4 exhibited smaller tumors and longer survival than those engrafted with control gastric cancer cells. These data indicated that ERBB4 promoted cell proliferation and is thus a potential therapeutic target for the treatment of gastric cancer.
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1 

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Ni CY, Murphy MP, Golde TE and Carpenter G: gamma-Secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase. Science. 294:2179–2181. 2001. View Article : Google Scholar : PubMed/NCBI

5 

Sordella R, Bell DW, Haber DA and Settleman J: Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science. 305:1163–1167. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Tan WL, Jain A, Takano A, Newell EW, Iyer NG, Lim WT, Tan EH, Zhai W, Hillmer AM, Tam WL, et al: Novel therapeutic targets on the horizon for lung cancer. Lancet Oncol. 17:e347–e362. 2016. View Article : Google Scholar : PubMed/NCBI

7 

Li M, Zhang Z, Li X, Ye J, Wu X, Tan Z, Liu C, Shen B, Wang XA, Wu W, et al: Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathway. Nat Genet. 46:872–876. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Arteaga CL and Engelman JA: ERBB receptors: From oncogene discovery to basic science to mechanism-based cancer therapeutics. Cancer Cell. 25:282–303. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Vlacich G and Coffey RJ: Resistance to EGFR-targeted therapy: A family affair. Cancer Cell. 20:423–425. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Hegde GV, de la Cruz CC, Chiu C, Alag N, Schaefer G, Crocker L, Ross S, Goldenberg D, Merchant M, Tien J, et al: Blocking NRG1 and other ligand-mediated Her4 signaling enhances the magnitude and duration of the chemotherapeutic response of non-small cell lung cancer. Sci Transl Med. 5:171ra182013. View Article : Google Scholar : PubMed/NCBI

11 

Settleman J: A therapeutic opportunity in melanoma: ErbB4 makes a mark on skin. Cancer Cell. 16:278–279. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Ma X, Li L, Tian T, Liu H, Li Q and Gao Q: Study of lung cancer regulatory network that involves erbB4 and tumor marker gene. Saudi J Biol Sci. 24:649–657. 2017. View Article : Google Scholar : PubMed/NCBI

13 

Broughton MN, Westgaard A, Paus E, Øijordsbakken M, Henanger KJ, Naume B and Bjøro T: Specific antibodies and sensitive immunoassays for the human epidermal growth factor receptors (HER2, HER3, and HER4). Tumour Biol. 39:10104283177074362017. View Article : Google Scholar : PubMed/NCBI

14 

Song G, Zhang H, Chen C, Gong L, Chen B, Zhao S, Shi J, Xu J and Ye Z: miR-551b regulates epithelial-mesenchymal transition and metastasis of gastric cancer by inhibiting ERBB4 expression. Oncotarget. 8:45725–45735. 2017.PubMed/NCBI

15 

Zhang M, Zhang L, Cui M, Ye W, Zhang P, Zhou S and Wang J: miR-302b inhibits cancer-related inflammation by targeting ERBB4, IRF2 and CXCR4 in esophageal cancer. Oncotarget. 8:49053–49063. 2017.PubMed/NCBI

16 

Ohashi Y, Kumagai K, Miyata Y, Matsubara R, Kitaura K, Suzuki S, Hamada Y and Suzuki R: Overexpression of ErbB4 is an independent marker for lymph node metastasis in Japanese patients with oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol. 122:313–321. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Ueda Y, Fujishima H, Hirashita T, Shiroshita H, Etoh T, Inomata M and Shiraishi N: Clinical impact of small advanced gastric cancer (≤40 mm) in elderly patients: A retrospective cohort study. Int J Surg. 45:131–137. 2017. View Article : Google Scholar : PubMed/NCBI

18 

Pereira MA, Ramos MFKP, Dias AR, Faraj SF, Yagi OK, Safatle-Ribeiro AV, Maluf-Filho F, Zilberstein B, Cecconello I, de Mello ES, et al: Risk factors for lymph node metastasis in western early gastric cancer after optimal surgical treatment. J Gastrointest Surg. 22:23–31. 2018. View Article : Google Scholar : PubMed/NCBI

19 

Chang JY, Shim KN, Tae CH, Lee KE, Lee J, Lee KH, Moon CM, Kim SE, Jung HK, Jung SA, et al: Comparison of clinical outcomes after endoscopic submucosal dissection and surgery in the treatment of early gastric cancer: A single-institute study. Medicine (Baltimore). 96:e72102017. View Article : Google Scholar : PubMed/NCBI

20 

Bang CS, Park JM, Baik GH, Park JJ, Joo MK, Jang JY, Jeon SW, Choi SC, Sung JK and Cho KB: Therapeutic outcomes of endoscopic resection of early gastric cancer with undifferentiated-type histology: A Korean ESD Registry Database analysis. Clin Endosc. 50:569–577. 2017. View Article : Google Scholar : PubMed/NCBI

21 

Pinto C, Di Fabio F, Barone C, Siena S, Falcone A, Cascinu S, Llimpe Rojas FL, Stella G, Schinzari G, Artale S, et al: Phase II study of cetuximab in combination with cisplatin and docetaxel in patients with untreated advanced gastric or gastro-oesophageal junction adenocarcinoma (DOCETUX study). Br J Cancer. 101:1261–1268. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Waddell T, Chau I, Cunningham D, Gonzalez D, Okines AF, Okines C, Wotherspoon A, Saffery C, Middleton G, Wadsley J, et al: Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): A randomised, open-label phase 3 trial. Lancet Oncol. 14:481–489. 2013. View Article : Google Scholar : PubMed/NCBI

23 

Sun GP, Sun Y, Xu RH, Xu JM, Li J, Wang JW, Qin S, Feng JF, Ba Y, Shen L, et al: The Chinese subgroup from a randomized phase III study of lapatinib in combination with weekly paclitaxel versus weekly paclitaxel alone as second-line treatment of HER2-amplified advanced gastric cancer (AGC) in Asian countries. J Clin Oncol. 31 Suppl:a41092013.

24 

Satoh T, Xu RH, Chung HC, Sun GP, Doi T, Xu JM, Tsuji A, Omuro Y, Li J, Wang JW, et al: Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTAN - a randomized, phase III study. J Clin Oncol. 32:2039–2049. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Lieto E, Ferraraccio F, Orditura M, Castellano P, Mura AL, Pinto M, Zamboli A, De Vita F and Galizia G: Expression of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) is an independent prognostic indicator of worse outcome in gastric cancer patients. Ann Surg Oncol. 15:69–79. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Chua TC and Merrett ND: Clinicopathologic factors associated with HER2-positive gastric cancer and its impact on survival outcomes - a systematic review. Int J Cancer. 130:2845–2856. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Hayashi M, Inokuchi M, Takagi Y, Yamada H, Kojima K, Kumagai J, Kawano T and Sugihara K: High expression of HER3 is associated with a decreased survival in gastric cancer. Clin Cancer Res. 14:7843–7849. 2008. View Article : Google Scholar : PubMed/NCBI

28 

Liu X, Zhou X, Xu H, He Z, Shi X and Wu S: SLC34A2 regulates the proliferation, migration, and invasion of human osteosarcoma cells through PTEN/PI3K/AKT signaling. DNA Cell Biol. 36:775–780, Epub ahead of print. 2017.PubMed/NCBI

29 

Liang L, Gao C, Li Y, Sun M, Xu J, Li H, Jia L and Zhao Y: miR-125a-3p/FUT5-FUT6 axis mediates colorectal cancer cell proliferation, migration, invasion and pathological angiogenesis via PI3K-Akt pathway. Cell Death Dis. 8:e29682017. View Article : Google Scholar : PubMed/NCBI

30 

Fruman DA, Snapper SB, Yballe CM, Davidson L, Yu JY, Alt FW and Cantley LC: Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85alpha. Science. 283:393–397. 1999. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Xu J, Gong L, Qian Z, Song G and Liu J: ERBB4 promotes the proliferation of gastric cancer cells via the PI3K/Akt signaling pathway. Oncol Rep 39: 2892-2898, 2018.
APA
Xu, J., Gong, L., Qian, Z., Song, G., & Liu, J. (2018). ERBB4 promotes the proliferation of gastric cancer cells via the PI3K/Akt signaling pathway. Oncology Reports, 39, 2892-2898. https://doi.org/10.3892/or.2018.6343
MLA
Xu, J., Gong, L., Qian, Z., Song, G., Liu, J."ERBB4 promotes the proliferation of gastric cancer cells via the PI3K/Akt signaling pathway". Oncology Reports 39.6 (2018): 2892-2898.
Chicago
Xu, J., Gong, L., Qian, Z., Song, G., Liu, J."ERBB4 promotes the proliferation of gastric cancer cells via the PI3K/Akt signaling pathway". Oncology Reports 39, no. 6 (2018): 2892-2898. https://doi.org/10.3892/or.2018.6343
Copy and paste a formatted citation
x
Spandidos Publications style
Xu J, Gong L, Qian Z, Song G and Liu J: ERBB4 promotes the proliferation of gastric cancer cells via the PI3K/Akt signaling pathway. Oncol Rep 39: 2892-2898, 2018.
APA
Xu, J., Gong, L., Qian, Z., Song, G., & Liu, J. (2018). ERBB4 promotes the proliferation of gastric cancer cells via the PI3K/Akt signaling pathway. Oncology Reports, 39, 2892-2898. https://doi.org/10.3892/or.2018.6343
MLA
Xu, J., Gong, L., Qian, Z., Song, G., Liu, J."ERBB4 promotes the proliferation of gastric cancer cells via the PI3K/Akt signaling pathway". Oncology Reports 39.6 (2018): 2892-2898.
Chicago
Xu, J., Gong, L., Qian, Z., Song, G., Liu, J."ERBB4 promotes the proliferation of gastric cancer cells via the PI3K/Akt signaling pathway". Oncology Reports 39, no. 6 (2018): 2892-2898. https://doi.org/10.3892/or.2018.6343
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