STMN1, a prognostic predictor of esophageal squamous cell carcinoma, is a marker of the activation of the PI3K pathway Corrigendum in /10.3892/or.2020.7855

Jiang,Wenpeng; Huang,Shiting; Song,Liang; Wang,Zhou

doi:10.3892/or.2017.6145

STMN1, a prognostic predictor of esophageal squamous cell carcinoma, is a marker of the activation of the PI3K pathway

Corrigendum in: /10.3892/or.2020.7855

Authors:
- Wenpeng Jiang
- Shiting Huang
- Liang Song
- Zhou Wang
View Affiliations

Affiliations: Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Shandong Medical Imaging Research Institute, Shandong University, Jinan, Shandong 250021, P.R. China
Published online on: December 11, 2017 https://doi.org/10.3892/or.2017.6145
Pages: 834-842

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

The esophageal squamous cell carcinoma (ESCC) subtype with STMN1 overexpression has a high likelihood of lymphatic metastatic recurrence. However, the underlying mechanism remains to be further elucidated. We assessed the expression level of STMN1 and PTEN in 96 pN0 ESCC patient tissues using immunohistochemistry and western blot analysis. Then, the association between STMN1 overexpression and postoperative lymphatic metastatic recurrence was evaluated. In addition, the relationship between STMN1 and PTEN was also assessed. The results showed that STMN1 expression was significantly higher in tumor tissues (P=0.013). STMN1 overexpression was related to tumor length (P=0.003) and depth of invasion (P=0.019). In addition, STMN1 overexpression was significantly associated with postoperative lymphatic metastatic recurrence in pN0 ESCC patients. Patients with STMN1-overexpressing tumors had a higher 3‑year lymphatic metastatic recurrence rate (P=0.024). Furthermore, in laboratory experiments, STMN1 expression was stably silenced using lentiviral vector delivery of shRNA in Eca109 and EC9706 cell lines to assess the functional effect of STMN1 in vitro. The results indicated that stable silencing of STMN1 expression significantly inhibited cell proliferation, migration and invasion. Moreover, we inactivated the PI3K pathway in ESCC cell lines with the PI3K inhibitor LY294002 and then detected STMN1 expression by western blot analysis. STMN1 levels were robustly reduced consistent with the downregulation of p‑Akt (S473) by PI3K pathway inhibition. STMN1 can act as a marker to quantitatively measure the activation of the PI3K pathway and stratify patients accordingly.

View Figures

View References

1	Napier KJ, Scheerer M and Misra S: Esophageal cancer: A review of epidemiology, pathogenesis, staging workup and treatment modalities. World J Gastrointest Oncol. 6:112–120. 2014. View Article : Google Scholar : PubMed/NCBI
2	Holmes RS and Vaughan TL: Epidemiology and pathogenesis of esophageal cancer. Semin Radiat Oncol. 17:2–9. 2007. View Article : Google Scholar : PubMed/NCBI
3	Dawsey SM, Lewin KJ, Liu FS, Wang GQ and Shen Q: Esophageal morphology from Linxian, China. Squamous histologic findings in 754 patients. Cancer. 73:2027–2037. 1994. View Article : Google Scholar : PubMed/NCBI
4	Cook MB: Non-acid reflux: The missing link between gastric atrophy and esophageal squamous cell carcinoma? Am J Gastroenterol. 106:1930–1932. 2011. View Article : Google Scholar : PubMed/NCBI
5	Zhang Y: Epidemiology of esophageal cancer. World J Gastroenterol. 19:5598–5606. 2013. View Article : Google Scholar : PubMed/NCBI
6	Doye V, Le Gouvello S, Dobransky T, Chneiweiss H, Beretta L and Sobel A: Expression of transfected stathmin cDNA reveals novel phosphorylated forms associated with developmental and functional cell regulation. Biochem J. 287:549–554. 1992. View Article : Google Scholar : PubMed/NCBI
7	Jeon TY, Han ME, Lee YW, Lee YS, Kim GH, Song GA, Hur GY, Kim JY, Kim HJ, Yoon S, et al: Overexpression of stathmin1 in the diffuse type of gastric cancer and its roles in proliferation and migration of gastric cancer cells. Br J Cancer. 102:710–718. 2010. View Article : Google Scholar : PubMed/NCBI
8	Bieche I, Lachkar S, Becette V, Cifuentes-Diaz C, Sobel A, Lidereau R and Curmi PA: Overexpression of the stathmin gene in a subset of human breast cancer. Br J Cancer. 78:701–709. 1998. View Article : Google Scholar : PubMed/NCBI
9	Rana S, Maples PB, Senzer N and Nemunaitis J: Stathmin 1: A novel therapeutic target for anticancer activity. Expert Rev Anticancer Ther. 8:1461–1470. 2008. View Article : Google Scholar : PubMed/NCBI
10	Akhtar J, Wang Z, Jiang WP, Bi MM and Zhang ZP: Stathmin overexpression identifies high risk for lymphatic metastatic recurrence in pN0 esophageal squamous cell carcinoma patients. J Gastroenterol Hepatol. 29:944–950. 2014. View Article : Google Scholar : PubMed/NCBI
11	Altomare DA and Testa JR: Perturbations of the AKT signaling pathway in human cancer. Oncogene. 24:7455–7464. 2005. View Article : Google Scholar : PubMed/NCBI
12	Vivanco I and Sawyers CL: The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer. 2:489–501. 2002. View Article : Google Scholar : PubMed/NCBI
13	Carnero A: The PKB/AKT pathway in cancer. Curr Pharm Des. 16:34–44. 2010. View Article : Google Scholar : PubMed/NCBI
14	Datta SR, Brunet A and Greenberg ME: Cellular survival: A play in three Akts. Genes Dev. 13:2905–2927. 1999. View Article : Google Scholar : PubMed/NCBI
15	Vanhaesebroeck B and Waterfield MD: Signaling by distinct classes of phosphoinositide 3-kinases. Exp Cell Res. 253:239–254. 1999. View Article : Google Scholar : PubMed/NCBI
16	Shi Y, Paluch BE, Wang X and Jiang X: PTEN at a glance. J Cell Sci. 125:4687–4692. 2012. View Article : Google Scholar : PubMed/NCBI
17	Saal LH, Johansson P, Holm K, Gruvberger-Saal SK, She QB, Maurer M, Koujak S, Ferrando AA, Malmström P, Memeo L, et al: Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity. Proc Natl Acad Sci USA. 104:pp. 7564–7569. 2007; View Article : Google Scholar : PubMed/NCBI
18	Chen J, Lan T, Zhang W, Dong L, Kang N, Fu M, Liu B, Liu K, Zhang C, Hou J and Zhan Q: Dasatinib enhances cisplatin sensitivity in human esophageal squamous cell carcinoma (ESCC) cells via suppression of PI3K/AKT and Stat3 pathways. Arch Biochem Biophys. 575:38–45. 2015. View Article : Google Scholar : PubMed/NCBI
19	Xu J and Hu Z: Y-box-binding protein 1 promotes tumor progression and inhibits cisplatin chemosensitivity in esophageal squamous cell carcinoma. Biomed Pharmacother. 79:17–22. 2016. View Article : Google Scholar : PubMed/NCBI
20	Jiang W, Wang Z and Jia Y: CEP55 overexpression predicts poor prognosis in patients with locally advanced esophageal squamous cell carcinoma. Oncol Lett. 13:236–242. 2017.PubMed/NCBI
21	Sun Z, Ji N, Bi M, Zhang Z, Liu X and Wang Z: Negative expression of PTEN identifies high risk for lymphatic-related metastasis in human esophageal squamous cell carcinoma. Oncol Rep. 33:3024–3032. 2015. View Article : Google Scholar : PubMed/NCBI
22	Akhtar J, Wang Z, Zhang ZP and Bi MM: Lentiviral-mediated RNA interference targeting stathmin1 gene in human gastric cancer cells inhibits proliferation in vitro and tumor growth in vivo. J Transl Med. 11:2122013. View Article : Google Scholar : PubMed/NCBI
23	Rice TW, Rusch VW, Ishwaran H and Blackstone EH; Worldwide Esophageal Cancer Collaboration, : Cancer of the esophagus and esophagogastric junction: Data-driven staging for the seventh edition of the American Joint Committee on Cancer/International Union against cancer cancer staging manuals. Cancer. 116:3763–3773. 2010. View Article : Google Scholar : PubMed/NCBI
24	Nieman DR and Peters JH: Treatment strategies for esophageal cancer. Gastroenterol Clin North Am. 42:187–197. 2013. View Article : Google Scholar : PubMed/NCBI
25	Fesik SW: Promoting apoptosis as a strategy for cancer drug discovery. Nat Rev Cancer. 5:876–885. 2005. View Article : Google Scholar : PubMed/NCBI
26	Cajone F and Sherbet GV: Stathmin is involved in S100A4-mediated regulation of cell cycle progression. Clin Exp Metastasis. 17:865–871. 1999. View Article : Google Scholar : PubMed/NCBI
27	Belletti B and Baldassarre G: Stathmin: A protein with many tasks. New biomarker and potential target in cancer. Expert Opin Ther Targets. 15:1249–1266. 2011. View Article : Google Scholar : PubMed/NCBI
28	Zhang C, Chakravarty D, Sakabe I, Mewani RR, Boudreau HE, Kumar D, Ahmad I and Kasid UN: Role of SCC-S2 in experimental metastasis and modulation of VEGFR-2, MMP-1, and MMP-9 expression. Mol Ther. 13:947–955. 2006. View Article : Google Scholar : PubMed/NCBI
29	Shaw RJ and Cantley LC: Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature. 441:424–430. 2006. View Article : Google Scholar : PubMed/NCBI
30	Janzen V and Scadden DT: Stem cells: Good, bad and reformable. Nature. 441:418–419. 2006. View Article : Google Scholar : PubMed/NCBI
31	Manning BD and Cantley LC: AKT/PKB signaling: Navigating downstream. Cell. 129:1261–1274. 2007. View Article : Google Scholar : PubMed/NCBI
32	Di Cristofano A and Pandolfi PP: The multiple roles of PTEN in tumor suppression. Cell. 100:387–390. 2000. View Article : Google Scholar : PubMed/NCBI
33	Shah A, Swain WA, Richardson D, Edwards J, Stewart DJ, Richardson CM, Swinson DE, Patel D, Jones JL and O'Byrne KJ: Phospho-akt expression is associated with a favorable outcome in non-small cell lung cancer. Clin Cancer Res. 11:2930–2936. 2005. View Article : Google Scholar : PubMed/NCBI
34	Tang JM, He QY, Guo RX and Chang XJ: Phosphorylated Akt overexpression and loss of PTEN expression in non-small cell lung cancer confers poor prognosis. Lung Cancer. 51:181–191. 2006. View Article : Google Scholar : PubMed/NCBI
35	Panigrahi AR, Pinder SE, Chan SY, Paish EC, Robertson JF and Ellis IO: The role of PTEN and its signalling pathways, including AKT, in breast cancer; an assessment of relationships with other prognostic factors and with outcome. J Pathol. 204:93–100. 2004. View Article : Google Scholar : PubMed/NCBI