TIPE1 impairs ovarian tumor growth by promoting caspase-dependent apoptosis

Li,Tingting; Jia,Lei; Deng,Yu; Wang,Bo; Quan,Song

doi:10.3892/ol.2020.12227

TIPE1 impairs ovarian tumor growth by promoting caspase-dependent apoptosis

Authors:
- Tingting Li
- Lei Jia
- Yu Deng
- Bo Wang
- Song Quan
View Affiliations

Affiliations: Department of Gynecology and Obstetrics, Center for Reproductive Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Reproductive Medicine Research Center, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510655, P.R. China, Assisted Reproductive Medical Center, Guangzhou Women and Children's Hospital, Guangzhou, Guangdong 510623, P.R. China
Published online on: October 15, 2020 https://doi.org/10.3892/ol.2020.12227
Article Number: 365
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Tumor necrosis factor‑α‑induced protein 8‑like 1 (TIPE1) functions as a tumor suppressor in several types of cancer, including lung and breast cancer. The present study aimed to determine the level of expression and the function of TIPE1 in ovarian cancer. TIPE1 expression was determined in tissue microarrays and ovarian cancer cells, and these data were analyzed to assess the association between TIPE1 expression and prognosis in patients with ovarian cancer. The potential antitumor effects of TIPE1 were investigated in vitro and in a xenograft mouse model. Furthermore, the underlying molecular mechanism by which TIPE1 regulates ovarian cancer growth was determined via flow cytometric analysis, western blotting and rescue experiments. The results of the present study indicated that TIPE1 levels were markedly decreased in ovarian cancer tissues, and its level of expression was associated with a favorable prognosis of patients with ovarian cancer. In addition, ectopic TIPE1 expression significantly impaired A2780 and SKOV3 cell proliferation and colony formation in vitro, which was accompanied by efficient inhibition of xenograft tumor growth in mice. Investigations into the underlying molecular mechanism demonstrated that TIPE1 induced ovarian cancer cell apoptosis by promoting caspase protein expression. Inhibition of caspase‑dependent apoptosis by z‑VAD blocked TIPE1‑mediated inhibition of the proliferation and induction of apoptosis in ovarian cancer cells. Collectively, the results of the present study suggest that TIPE1 may be a potential prognostic predictor and therapeutic target for patients with ovarian cancer.

View Figures

View References

1	Torre LA, Trabert B, DeSantis CE, Miller KD, Samimi G, Runowicz CD, Gaudet MM, Jemal A and Siegel RL: Ovarian cancer statistics, 2018. CA Cancer J Clin. 68:284–296. 2018. View Article : Google Scholar : PubMed/NCBI
2	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2020. CA Cancer J Clin. 70:7–30. 2020. View Article : Google Scholar : PubMed/NCBI
3	Lheureux S, Braunstein M and Oza AM: Epithelial ovarian cancer: Evolution of management in the era of precision medicine. CA Cancer J Clin. 69:280–304. 2019.PubMed/NCBI
4	Partridge EE and Barnes MN: Epithelial ovarian cancer: Prevention, diagnosis, and treatment. CA Cancer J Clin. 49:297–320. 1999. View Article : Google Scholar : PubMed/NCBI
5	Kim JY, Cho CH and Song HS: Targeted therapy of ovarian cancer including immune check point inhibitor. Korean J Intern Med (Korean Assoc Intern Med). 32:798–804. 2017.
6	Kroeger PT Jr and Drapkin R: Pathogenesis and heterogeneity of ovarian cancer. Curr Opin Obstet Gynecol. 29:26–34. 2017. View Article : Google Scholar : PubMed/NCBI
7	Dong X, Men X, Zhang W and Lei P: Advances in tumor markers of ovarian cancer for early diagnosis. Indian J Cancer. 51 (Suppl 3):e72–e76. 2014. View Article : Google Scholar : PubMed/NCBI
8	Yang WL, Lu Z and Bast RC Jr: The role of biomarkers in the management of epithelial ovarian cancer. Expert Rev Mol Diagn. 17:577–591. 2017. View Article : Google Scholar : PubMed/NCBI
9	Bordoloi D, Banik K, Shabnam B, Padmavathi G, Monisha J, Arfuso F, Dharmarajan A, Mao X, Lim LHK, Wang L, et al: TIPE family of proteins and its implications in different chronic diseases. Int J Mol Sci. 19:192018. View Article : Google Scholar
10	Jiang J, Pang X, Liu H, Yang X, Zhang Y, Xiang X, Li J, Li T and Zhao P: Reduced TIPE2 expression is inversely associated with proinflammatory cytokines and positively correlated with bone mineral density in patients with osteoporosis. Life Sci. 216:227–232. 2019. View Article : Google Scholar : PubMed/NCBI
11	Wang Q, Ma L, Liu T, Ge C, Zhou Q, Wei C and Shi W: TIPE2 suppresses Pseudomonas aeruginosa keratitis by inhibiting NF-kappaB signaling and the infiltration of inflammatory cells. J Infect Dis. 220:1008–1018. 2019. View Article : Google Scholar : PubMed/NCBI
12	Liu Y, Ni XY, Chen RL, Li J and Gao FG: TIPE attenuates the apoptotic effect of radiation and cisplatin and promotes tumor growth via JNK and p38 activation in Raw264.7 and EL4 cells. Oncol Rep. 39:2688–2694. 2018.PubMed/NCBI
13	Padmavathi G, Banik K, Monisha J, Bordoloi D, Shabnam B, Arfuso F, Sethi G, Fan L and Kunnumakkara AB: Novel tumor necrosis factor-α induced protein eight (TNFAIP8/TIPE) family: Functions and downstream targets involved in cancer progression. Cancer Lett. 432:260–271. 2018. View Article : Google Scholar : PubMed/NCBI
14	Zhang Z, Liang X, Gao L, Ma H, Liu X, Pan Y, Yan W, Shan H, Wang Z, Chen YH, et al: TIPE1 induces apoptosis by negatively regulating Rac1 activation in hepatocellular carcinoma cells. Oncogene. 34:2566–2574. 2015. View Article : Google Scholar : PubMed/NCBI
15	Wu X, Ma Y, Cheng J, Li X, Zheng H, Jiang L and Zhou R: TIPE1 function as a prognosis predictor and negative regulator of lung cancer. Oncotarget. 8:78496–78506. 2017. View Article : Google Scholar : PubMed/NCBI
16	Liu W, Chen Y, Xie H, Guo Y, Ren D, Li Y, Jing X, Li D, Wang X, Zhao M, et al: TIPE1 suppresses invasion and migration through down-regulating Wnt/β-catenin pathway in gastric cancer. J Cell Mol Med. 22:1103–1117. 2018.PubMed/NCBI
17	Zhao P, Pang X, Jiang J, Wang L, Zhu X, Yin Y, Zhai Q, Xiang X, Feng F and Xu W: TIPE1 promotes cervical cancer progression by repression of p53 acetylation and is associated with poor cervical cancer outcome. Carcinogenesis. 40:592–599. 2019. View Article : Google Scholar : PubMed/NCBI
18	Chen P, Zhou J, Li J, Zhang Q and Zuo Q: TIPE1 suppresses osteosarcoma tumor growth by regulating macrophage infiltration. Clin Transl Oncol. 21:334–341. 2019. View Article : Google Scholar : PubMed/NCBI
19	Dai L, Cui X, Zhang X, Cheng L, Liu Y, Yang Y, Fan P, Wang Q, Lin Y, Zhang J, et al: SARI inhibits angiogenesis and tumour growth of human colon cancer through directly targeting ceruloplasmin. Nat Commun. 7:119962016. View Article : Google Scholar : PubMed/NCBI
20	Ujiie D, Okayama H, Saito K, Ashizawa M, Min AK, Endo E, Kase K, Yamada L, Kikuchi T, Hanayama H, et al: KRT17 as a prognostic biomarker for stage II colorectal cancer. Carcinogenesis. 41:591–599. 2020. View Article : Google Scholar : PubMed/NCBI
21	Bao L, You B, Shi S, Shan Y, Zhang Q, Yue H, Zhang J, Zhang W, Shi Y, Liu Y, et al: Metastasis-associated miR-23a from nasopharyngeal carcinoma-derived exosomes mediates angiogenesis by repressing a novel target gene TSGA10. Oncogene. 37:2873–2889. 2018. View Article : Google Scholar : PubMed/NCBI
22	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
23	Cui J, Zhang G, Hao C, Wang Y, Lou Y, Zhang W, Wang J and Liu S: The expression of TIPE1 in murine tissues and human cell lines. Mol Immunol. 48:1548–1555. 2011. View Article : Google Scholar : PubMed/NCBI
24	Wang Y, Liu Y, Hu C, Ni X and Huang X: Tumor necrosis factor α-induced protein 8-like 1 promotes apoptosis by regulating B-cell leukemia/lymphoma-2 family proteins in RAW264.7 cells. Oncol Lett. 12:3506–3512. 2016. View Article : Google Scholar : PubMed/NCBI
25	Luan YY, Zhang L, Zhu FJ, Dong N, Lu JY and Yao YM: Effect of TIPE1 on immune function of dendritic cells and its signaling pathway in septic mice. J Infect Dis. 220:699–709. 2019. View Article : Google Scholar : PubMed/NCBI
26	Ye T, Yang B, Wang C, Su C, Luo J, Yang X, Yu H, Yuan Z, Meng Z and Xia J: TIPE1 impairs stemness maintenance in colorectal cancer through directly targeting β-catenin. Carcinogenesis. 41:25–35. 2020.PubMed/NCBI
27	Hu W, Feng CM, Liu LY, Li N, Tian F, Du JX, Zhao Y, Xiang XX, Liu K and Zhao PQ: TIPE1 inhibits breast cancer proliferation by downregulating ERK phosphorylation and predicts a favorable prognosis. Front Oncol. 9:4002019. View Article : Google Scholar : PubMed/NCBI
28	Tong Y, Zhang G, Li Y, Xu J, Yuan J, Zhang B, Hu T and Song G: Corilagin inhibits breast cancer growth via reactive oxygen species-dependent apoptosis and autophagy. J Cell Mol Med. 22:3795–3807. 2018. View Article : Google Scholar
29	Yan XY, Zhong XR, Yu SH, Zhang LC, Liu YN, Zhang Y, Sun LK and Su J: p62 aggregates mediated caspase 8 activation is responsible for progression of ovarian cancer. J Cell Mol Med. 23:4030–4042. 2019. View Article : Google Scholar : PubMed/NCBI
30	Seo JA, Kim B, Dhanasekaran DN, Tsang BK and Song YS: Curcumin induces apoptosis by inhibiting sarco/endoplasmic reticulum Ca²⁺ ATPase activity in ovarian cancer cells. Cancer Lett. 371:30–37. 2016. View Article : Google Scholar : PubMed/NCBI
31	Wang H, Luo Y, Qiao T, Wu Z and Huang Z: Luteolin sensitizes the antitumor effect of cisplatin in drug-resistant ovarian cancer via induction of apoptosis and inhibition of cell migration and invasion. J Ovarian Res. 11:932018. View Article : Google Scholar : PubMed/NCBI