Tropomyosin-1 promotes cancer cell apoptosis via the p53-mediated mitochondrial pathway in renal cell carcinoma

Tang,Chao; Wang,Jin; Wei,Qi; Du,Yi‑Peng; Qiu,He‑Ping; Yang,Chao; Hou,Yu‑Chuan

doi:10.3892/ol.2018.8204

Tropomyosin-1 promotes cancer cell apoptosis via the p53-mediated mitochondrial pathway in renal cell carcinoma

Authors:
- Chao Tang
- Jin Wang
- Qi Wei
- Yi‑Peng Du
- He‑Ping Qiu
- Chao Yang
- Yu‑Chuan Hou
View Affiliations

Affiliations: Department of Urology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Anesthesiology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: March 7, 2018 https://doi.org/10.3892/ol.2018.8204
Pages: 7060-7068
Copyright: © Tang 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

Tropomyosin-1 (TPM1), a widely expressed actin‑binding protein, is downregulated in many tumors and associated with cancer progression. A previous study from our group suggested that TPM1 could be involved in renal cell carcinoma (RCC) apoptosis, but the mechanisms and details remained unknown. The present study aimed to further examine the proapoptotic effects of TPM1 and investigate the underlying mechanisms in RCC cell lines. Results from cell viability, DAPI staining and apoptosis assays demonstrated that TPM1 upregulation inhibited cell proliferation and promoted cell apoptosis in both 786‑O and ACHN RCC cell lines. However, TPM1 knockdown in the two RCC cell lines did not result in the opposite effects on cell proliferation or cell apoptosis. Comet assay and western blotting results demonstrated that TPM1 overexpression induced DNA damage and decreased the expression levels of the antiapoptotic factor BCL2 apoptosis regulator, while increasing the expression levels of the proapoptotic factors BCL2 associated X, Caspase‑3 and p53 in 786‑O and ACHN cells. The present findings suggest that TPM1 overexpression in RCC cell lines can induce tumor cell apoptosis via the p53‑mediated mitochondrial pathway. Further studies are needed to fully elucidate the potential of TPM1 as a candidate for RCC targeted therapy in the future.

View Figures

View References

1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016. View Article : Google Scholar : PubMed/NCBI
2	Chen W, Zheng R, Zhang S, Zeng H, Xia C, Zuo T, Yang Z, Zou X and He J: Cancer incidence and mortality in China, 2013. Cancer Lett. 401:63–71. 2017. View Article : Google Scholar : PubMed/NCBI
3	Turner RM II, Morgan TM and Jacobs BL: Epidemiology of the Small Renal Mass and the treatment disconnect phenomenon. Urol Clin North Am. 44:147–154. 2017. View Article : Google Scholar : PubMed/NCBI
4	Perry SV: Vertebrate tropomyosin: Distribution, properties and function. J Muscle Res Cell Motil. 22:5–49. 2001. View Article : Google Scholar : PubMed/NCBI
5	Helfman DM, Flynn P, Khan P and Saeed A: Tropomyosin as a regulator of cancer cell transformation. Adv Exp Med Biol. 644:124–131. 2008. View Article : Google Scholar : PubMed/NCBI
6	Bharadwaj S and Prasad GL: Tropomyosin-1, a novel suppressor of cellular transformation is down regulated by promoter methylation in cancer cells. Cancer Lett. 183:205–213. 2002. View Article : Google Scholar : PubMed/NCBI
7	Petrova DT, Asif AR, Armstrong VW, Dimova I, Toshev S, Yaramov N, Oellerich M and Toncheva D: Expression of chloride intracellular channel protein 1 (CLIC1) and tumor protein D52 (TPD52) as potential biomarkers for colorectal cancer. Clin Biochem. 41:1224–1236. 2008. View Article : Google Scholar : PubMed/NCBI
8	Ku BM, Ryu HW, Lee YK, Ryu J, Jeong JY, Choi J, Cho HJ, Park KH and Kang SS: 4′-Acetoamido-4-hydroxychalcone, a chalcone derivative, inhibits glioma growth and invasion through regulation of the tropomyosin 1 gene. Biochem Biophys Res Commun. 402:525–530. 2010. View Article : Google Scholar : PubMed/NCBI
9	Yager ML, Hughes JA, Lovicu FJ, Gunning PW, Weinberger RP and O'Neill GM: Functional analysis of the actin-binding protein, tropomyosin 1, in neuroblastoma. Br J Cancer. 89:860–863. 2003. View Article : Google Scholar : PubMed/NCBI
10	Wang J, Guan J, Lu Z, Jin J, Cai Y, Wang C and Wang F: Clinical and tumor significance of tropomyosin-1 expression levels in renal cell carcinoma. Oncol Rep. 33:1326–1334. 2015. View Article : Google Scholar : PubMed/NCBI
11	Pan H, Gu L, Liu B, Li Y, Wang Y, Bai X, Li L, Wang B, Peng Q, Yao Z and Tang Z: Tropomyosin-1 acts as a potential tumor suppressor in human oral squamous cell carcinoma. PLoS One. 12:e01689002017. View Article : Google Scholar : PubMed/NCBI
12	Yang W, Wang X, Zheng W, Li K, Liu H and Sun Y: Genetic and epigenetic alterations are involved in the regulation of TPM1 in cholangiocarcinoma. Int J Oncol. 42:690–698. 2013. View Article : Google Scholar : PubMed/NCBI
13	England J, Granados-Riveron J, Polo-Parada L, Kuriakose D, Moore C, Brook JD, Rutland CS, Setchfield K, Gell C, Ghosh TK, et al: Tropomyosin 1: Multiple roles in the developing heart and in the formation of congenital heart defects. J Mol Cell Cardiol. 106:1–13. 2017. View Article : Google Scholar : PubMed/NCBI
14	Lv L, Huang F, Mao H, Li M, Li X, Yang M and Yu X: MicroRNA-21 is overexpressed in renal cell carcinoma. Int J Biol Markers. 28:201–207. 2013. View Article : Google Scholar : PubMed/NCBI
15	Zhu S, Si ML, Wu H and Mo YY: MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem. 282:14328–14336. 2007. View Article : Google Scholar : PubMed/NCBI
16	Zhu S, Wu H, Wu F, Nie D, Sheng S and Mo YY: MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res. 18:350–359. 2008. View Article : Google Scholar : PubMed/NCBI
17	Wang Y, Gao X, Wei F, Zhang X, Yu J, Zhao H, Sun Q, Yan F, Yan C, Li H and Ren X: Diagnostic and prognostic value of circulating miR-21 for cancer: A systematic review and meta-analysis. Gene. 533:389–397. 2014. View Article : Google Scholar : PubMed/NCBI
18	Sekar D, Krishnan R, Thirugnanasambantham K, Rajasekaran B, Islam VI and Sekar P: Significance of microRNA 21 in gastric cancer. Clin Res Hepatol Gastroenterol. 40:538–545. 2016. View Article : Google Scholar : PubMed/NCBI
19	Jin ZY and El-Deiry WS: Overview of cell death signaling pathways. Cancer Biol Ther. 4:139–163. 2005. View Article : Google Scholar : PubMed/NCBI
20	Breckenridge DG, Germain M, Mathai JP, Nguyen M and Shore GC: Regulation of apoptosis by endoplasmic reticulum pathways. Oncogene. 22:8608–8618. 2003. View Article : Google Scholar : PubMed/NCBI
21	Newmeyer DD and Ferguson-Miller S: Mitochondria: Releasing power for life and unleashing the machineries of death. Cell. 112:481–490. 2003. View Article : Google Scholar : PubMed/NCBI
22	Pradelli LA, Bénéteau M and Ricci JE: Mitochondrial control of caspase-dependent and -independent cell death. Cell Mol Life Sci. 67:1589–1597. 2010. View Article : Google Scholar : PubMed/NCBI
23	Tait SW and Green DR: Mitochondrial regulation of cell death. Cold Spring Harb Perspect Biol. 5:pii:a0087062013. View Article : Google Scholar
24	Ashkenazi A and Dixit VM: Death receptors: Signaling and modulation. Science. 281:1305–1308. 1998. View Article : Google Scholar : PubMed/NCBI
25	Dashzeveg N and Yoshida K: Cell death decision by p53 via control of the mitochondrial membrane. Cancer Lett. 367:108–112. 2015. View Article : Google Scholar : PubMed/NCBI
26	Glab JA, Doerflinger M, Nedeva C, Jose I, Mbogo GW, Paton JC, Paton AW, Kueh AJ, Herold MJ, Huang DC, et al: DR5 and caspase-8 are dispensable in ER stress-induced apoptosis. Cell Death Differ. 24:944–950. 2017. View Article : Google Scholar : PubMed/NCBI