Upregulated CTHRC1 promotes human epithelial ovarian cancer invasion through activating EGFR signaling

  • Authors:
    • Jun Ye
    • Wei Chen
    • Zhi-Yong Wu
    • Jin-Hui Zhang
    • He Fei
    • Li-Wen Zhang
    • Ya-Hui Wang
    • Ya-Ping Chen
    • Xiao-Mei Yang
  • View Affiliations

  • Published online on: October 24, 2016     https://doi.org/10.3892/or.2016.5198
  • Pages: 3588-3596
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Abstract

Epithelial ovarian cancer (EOC) is the major cause of deaths from gynecologic malignancies, and metastasis is the main cause of cancer related death. Collagen triple helix repeat containing-1 (CTHRC1) is a secreted protein that has the ability to inhibit collagen matrix synthesis. In this study, we found that high CTHRC1 expression was associated with poor prognosis of EOC. In vitro experiments showed that CTHRC1 promoted migration and invasion of ovarian cancer cells. CTHRC1 had no effect on ovarian cancer cells viability. Additionally, EGFR inhibitors reduced the promotion effects of CTHRC1 on EOC cell invasion. After silencing of CTHRC1, downregulated expression of phosphorylation of EGFR/ERK1/2/AKT was observed in ovarian cancer cells. Taken together, our results suggest a role for CTHRC1 in the progression of ovarian cancer and identified CTHRC1 as a potentially important predictor for human ovarian cancer prognosis.

References

1 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Alonso DF, Ripoll GV, Garona J, Iannucci NB and Gomez DE: Metastasis: Recent discoveries and novel perioperative treatment strategies with particular interest in the hemostatic compound desmopressin. Curr Pharm Biotechnol. 12:1974–1980. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Rhim AD, Mirek ET, Aiello NM, Maitra A, Bailey JM, McAllister F, Reichert M, Beatty GL, Rustgi AK, Vonderheide RH, et al: EMT and dissemination precede pancreatic tumor formation. Cell. 148:349–361. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Wu Z, Wu Z, Li J, Yang X, Wang Y, Yu Y, Ye J, Xu C, Qin W and Zhang Z: MCAM is a novel metastasis marker and regulates spreading, apoptosis and invasion of ovarian cancer cells. Tumour Biol. 33:1619–1628. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Durmus T, LeClair RJ, Park KS, Terzic A, Yoon JK and Lindner V: Expression analysis of the novel gene collagen triple helix repeat containing-1 (Cthrc1). Gene Expr Patterns. 6:935–940. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Tang L, Dai DL, Su M, Martinka M, Li G and Zhou Y: Aberrant expression of collagen triple helix repeat containing 1 in human solid cancers. Clin Cancer Res. 12:3716–3722. 2006. View Article : Google Scholar : PubMed/NCBI

7 

Wang P, Wang YC, Chen XY, Shen ZY, Cao H, Zhang YJ, Yu J, Zhu JD, Lu YY and Fang JY: CTHRC1 is upregulated by promoter demethylation and transforming growth factor-β1 and may be associated with metastasis in human gastric cancer. Cancer Sci. 103:1327–1333. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Ke Z, He W, Lai Y, Guo X, Chen S, Li S, Wang Y and Wang L: Overexpression of collagen triple helix repeat containing 1 (CTHRC1) is associated with tumour aggressiveness and poor prognosis in human non-small cell lung cancer. Oncotarget. 5:9410–9424. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Chan JK, Pham H, You XJ, Cloven NG, Burger RA, Rose GS, Van Nostrand K, Korc M, Disaia PJ and Fan H: Suppression of ovarian cancer cell tumorigenicity and evasion of cisplatin resistance using a truncated epidermal growth factor receptor in a rat model. Cancer Res. 65:3243–3248. 2005.PubMed/NCBI

10 

Phelps SL Bull, Schorge JO, Peyton MJ, Shigematsu H, Xiang LL, Miller DS and Lea JS: Implications of EGFR inhibition in ovarian cancer cell proliferation. Gynecol Oncol. 109:411–417. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Seshacharyulu P, Ponnusamy MP, Haridas D, Jain M, Ganti AK and Batra SK: Targeting the EGFR signaling pathway in cancer therapy. Expert Opin Ther Targets. 16:15–31. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Maihle NJ, Baron AT, Barrette BA, Boardman CH, Christensen TA, Cora EM, Faupel-Badger JM, Greenwood T, Juneja SC, Lafky JM, et al: EGF/ErbB receptor family in ovarian cancer. Cancer Treat Res. 107:247–258. 2002.PubMed/NCBI

13 

Zhou C, Qiu L, Sun Y, Healey S, Wanebo H, Kouttab N, Di W, Yan B and Wan Y: Inhibition of EGFR/PI3K/AKT cell survival pathway promotes TSA's effect on cell death and migration in human ovarian cancer cells. Int J Oncol. 29:269–278. 2006.PubMed/NCBI

14 

Loganathan S, Kandala PK, Gupta P and Srivastava SK: Inhibition of EGFR-AKT axis results in the suppression of ovarian tumors in vitro and in preclinical mouse model. PLoS One. 7:e435772012. View Article : Google Scholar : PubMed/NCBI

15 

Gan Y, Shi C, Inge L, Hibner M, Balducci J and Huang Y: Differential roles of ERK and Akt pathways in regulation of EGFR-mediated signaling and motility in prostate cancer cells. Oncogene. 29:4947–4958. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Hwang YP, Yun HJ, Choi JH, Han EH, Kim HG, Song GY, Kwon KI, Jeong TC and Jeong HG: Suppression of EGF-induced tumor cell migration and matrix metalloproteinase-9 expression by capsaicin via the inhibition of EGFR-mediated FAK/Akt, PKC/Raf/ERK, p38 MAPK, and AP-1 signaling. Mol Nutr Food Res. 55:594–605. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Hou M, Cheng Z, Shen H, He S, Li Y, Pan Y, Feng C, Chen X, Zhang Y, Lin M, et al: High expression of CTHRC1 promotes EMT of epithelial ovarian cancer (EOC) and is associated with poor prognosis. Oncotarget. 6:35813–35829. 2015.PubMed/NCBI

18 

Zhou X, Hu Y, Dai L, Wang Y, Zhou J, Wang W, Di W and Qiu L: MicroRNA-7 inhibits tumor metastasis and reverses epithelial-mesenchymal transition through AKT/ERK1/2 inactivation by targeting EGFR in epithelial ovarian cancer. PLoS One. 9:e967182014. View Article : Google Scholar : PubMed/NCBI

19 

Cao C, Lu S, Sowa A, Kivlin R, Amaral A, Chu W, Yang H, Di W and Wan Y: Priming with EGFR tyrosine kinase inhibitor and EGF sensitizes ovarian cancer cells to respond to chemotherapeutical drugs. Cancer Lett. 266:249–262. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Khalil I, Brewer MA, Neyarapally T and Runowicz CD: The potential of biologic network models in understanding the etiopathogenesis of ovarian cancer. Gynecol Oncol. 116:282–285. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Kharaishvili G, Cizkova M, Bouchalova K, Mgebrishvili G, Kolar Z and Bouchal J: Collagen triple helix repeat containing 1 protein, periostin and versican in primary and metastatic breast cancer: An immunohistochemical study. J Clin Pathol. 64:977–982. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Ma MZ, Zhuang C, Yang XM, Zhang ZZ, Ma H, Zhang WM, You H, Qin W, Gu J, Yang S, et al: CTHRC1 acts as a prognostic factor and promotes invasiveness of gastrointestinal stromal tumors by activating Wnt/PCP-Rho signaling. Neoplasia. 16:265–278, 278.e1-278.e13. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Kim HC, Kim YS, Oh HW, Kim K, Oh SS, Kim JT, Kim BY, Lee SJ, Choe YK, Kim DH, et al: Collagen triple helix repeat containing 1 (CTHRC1) acts via ERK-dependent induction of MMP9 to promote invasion of colorectal cancer cells. Oncotarget. 5:519–529. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Park EH, Kim S, Jo JY, Kim SJ, Hwang Y, Kim JM, Song SY, Lee DK and Koh SS: Collagen triple helix repeat containing-1 promotes pancreatic cancer progression by regulating migration and adhesion of tumor cells. Carcinogenesis. 34:694–702. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Nicholson RI, Gee JM and Harper ME: EGFR and cancer prognosis. Eur J Cancer. 37:(Suppl 4). S9–S15. 2001. View Article : Google Scholar : PubMed/NCBI

26 

Han M, Liu M, Wang Y, Chen X, Xu J, Sun Y, Zhao L, Qu H, Fan Y and Wu C: Antagonism of miR-21 reverses epithelial-mesenchymal transition and cancer stem cell phenotype through AKT/ERK1/2 inactivation by targeting PTEN. PLoS One. 7:e395202012. View Article : Google Scholar : PubMed/NCBI

27 

Chang ZG, Wei JM, Qin CF, Hao K, Tian XD, Xie K, Xie XH and Yang YM: Suppression of the epidermal growth factor receptor inhibits epithelial-mesenchymal transition in human pancreatic cancer PANC-1 cells. Dig Dis Sci. 57:1181–1189. 2012. View Article : Google Scholar : PubMed/NCBI

28 

Konishi H, Takagi A, Kurita A, Kaneda N and Matsuzaki T: PEGylated liposome IHL-305 markedly improved the survival of ovarian cancer peritoneal metastasis in mouse. BMC Cancer. 12:4622012. View Article : Google Scholar : PubMed/NCBI

29 

Wittinger M, Vanhara P, El-Gazzar A, Savarese-Brenner B, Pils D, Anees M, Grunt TW, Sibilia M, Holcmann M, Horvat R, et al: hVps37A status affects prognosis and cetuximab sensitivity in ovarian cancer. Clin Cancer Res. 17:7816–7827. 2011. View Article : Google Scholar : PubMed/NCBI

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December 2016
Volume 36 Issue 6

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APA
Ye, J., Chen, W., Wu, Z., Zhang, J., Fei, H., Zhang, L. ... Yang, X. (2016). Upregulated CTHRC1 promotes human epithelial ovarian cancer invasion through activating EGFR signaling. Oncology Reports, 36, 3588-3596. https://doi.org/10.3892/or.2016.5198
MLA
Ye, J., Chen, W., Wu, Z., Zhang, J., Fei, H., Zhang, L., Wang, Y., Chen, Y., Yang, X."Upregulated CTHRC1 promotes human epithelial ovarian cancer invasion through activating EGFR signaling". Oncology Reports 36.6 (2016): 3588-3596.
Chicago
Ye, J., Chen, W., Wu, Z., Zhang, J., Fei, H., Zhang, L., Wang, Y., Chen, Y., Yang, X."Upregulated CTHRC1 promotes human epithelial ovarian cancer invasion through activating EGFR signaling". Oncology Reports 36, no. 6 (2016): 3588-3596. https://doi.org/10.3892/or.2016.5198