CHST15 promotes the proliferation of TE‑1 cells via multiple pathways in esophageal cancer

Wang,Xin; Cheng,Guowei; Zhang,Tao; Deng,Lei; Xu,Kunpeng; Xu,Xin; Wang,Wenqing; Zhou,Zongmei; Feng,Qinfu; Chen,Dongfu; Bi,Nan; Wang,Luhua

doi:10.3892/or.2019.7395

CHST15 promotes the proliferation of TE‑1 cells via multiple pathways in esophageal cancer

Authors:
- Xin Wang
- Guowei Cheng
- Tao Zhang
- Lei Deng
- Kunpeng Xu
- Xin Xu
- Wenqing Wang
- Zongmei Zhou
- Qinfu Feng
- Dongfu Chen
- Nan Bi
- Luhua Wang
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Affiliations: Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China, Department of Radiotherapy, Huanxing Tumor Hospital, Beijing 100023, P.R. China, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, Guangdong 518116, P.R. China
Published online on: October 30, 2019 https://doi.org/10.3892/or.2019.7395
Pages: 75-86
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Esophageal squamous cell carcinoma (ESCC) is a common type of esophageal cancer and is prevalent worldwide. Understanding the mechanisms underlying its formation and the search for more effective therapeutic strategies are critical due to the occurrence of chemotherapeutic drug resistance. The aim of the present study was to determine the functional relevance and therapeutic potential of carbohydrate sulfotransferase 15 (CHST15) in ESCC. CHST15 levels were measured in different ESCC cell lines and evaluated in ESCC tissues using tissue chip immunohistochemistry. Cell growth and apoptosis assays, 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assays, and clonogenic assays were conducted using TE‑1 cells and lenti‑shCHST15 virus constructs were used to investigate the function of CHST15 in cell proliferation and apoptosis. mRNA microarray analysis was performed to determine the underlying mechanism of CHST15 regulation in TE‑1 cell proliferation and apoptosis. The results showed that knockdown of CHST15 inhibited TE‑1 cell growth and proliferation, but induced cell apoptosis. CHST15 was more frequently detected in ESCC tissue compared with that in normal esophageal tissue. Microarray data analysis indicated that the inhibition of cell proliferation and activation of cell apoptosis in CHST15‑knockdown cells may be caused by altered CHST15/ILKAP/CCND1 and CHST15/RABL6/PMAIP1 signaling axes, respectively.

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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	Domper Arnal MJ, Ferrández Arenas Á and Lanas Arbeloa Á: Esophageal cancer: Risk factors, screening and endoscopic treatment in Western and Eastern countries. World J Gastroenterol. 21:7933–7943. 2015. View Article : Google Scholar : PubMed/NCBI
3	Pennathur A, Gibson MK, Jobe BA and Luketich JD: Oesophageal carcinoma. Lancet. 381:400–412. 2013. View Article : Google Scholar : PubMed/NCBI
4	Wang J, Yu JM, Jing SW, Guo Y, Wu YJ, Li N, Jiao WP, Wang L and Zhang YJ: Relationship between EGFR over-expression and clinicopathologic characteristics in squamous cell carcinoma of the esophagus: A meta-analysis. Asian Pac J Cancer Prev. 15:5889–5893. 2014. View Article : Google Scholar : PubMed/NCBI
5	Hirashima K, Baba Y, Watanabe M, Karashima R, Sato N, Imamura Y, Hiyoshi Y, Nagai Y, Hayashi N, Iyama K and Baba H: Phosphorylated mTOR expression is associated with poor prognosis for patients with esophageal squamous cell carcinoma. Ann Surg Oncol. 17:2486–2493. 2010. View Article : Google Scholar : PubMed/NCBI
6	Takayama T, Nagao M, Sawada H, Yamada Y, Emoto K, Fujimoto H, Ueno M, Hirao S and Nakajima Y: Bcl-X expression in esophageal squamous cell carcinoma: Association with tumor progression and prognosis. J Surg Oncol. 78:116–123. 2001. View Article : Google Scholar : PubMed/NCBI
7	Nagaraja V and Eslick GD: Forthcoming prognostic markers for esophageal cancer: A systematic review and meta-analysis. J Gastrointest Oncol. 5:67–76. 2014.PubMed/NCBI
8	Cheng X, Wei L, Huang X, Zheng J, Shao M, Feng T, Li J, Han Y, Tan W, Tan W, et al: Solute carrier family 39 member 6 gene promotes aggressiveness of esophageal carcinoma cells by increasing intracellular levels of zinc, activating phosphatidylinositol 3-kinase signaling, and up-regulating genes that regulate metastasis. Gastroenterology. 152:1985–1997.e1912. 2017. View Article : Google Scholar : PubMed/NCBI
9	Jang HJ, Lee HS, Burt BM, Lee GK, Yoon KA, Park YY, Sohn BH, Kim SB, Kim MS, Lee JM, et al: Integrated genomic analysis of recurrence-associated small non-coding RNAs in oesophageal cancer. Gut. 66:215–225. 2017. View Article : Google Scholar : PubMed/NCBI
10	Wang L, Yu X, Zhang Z, Pang L, Xu J, Jiang J, Liang W, Chai Y, Hou J and Li F: Linc-ROR promotes esophageal squamous cell carcinoma progression through the derepression of SOX9. J Exp Clin Cancer Res. 36:1822017. View Article : Google Scholar : PubMed/NCBI
11	Yokoyama A, Kakiuchi N, Yoshizato T, Nannya Y, Suzuki H, Takeuchi Y, Shiozawa Y, Sato Y, Aoki K, Kim SK, et al: Age-related remodelling of oesophageal epithelia by mutated cancer drivers. Nature. 565:312–317. 2019. View Article : Google Scholar : PubMed/NCBI
12	Ohtake S, Ito Y, Fukuta M and Habuchi O: Human N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase cDNA is related to human B cell recombination activating gene-associated gene. J Biol Chem. 276:43894–43900. 2001. View Article : Google Scholar : PubMed/NCBI
13	Takakura K, Shibazaki Y, Yoneyama H, Fujii M, Hashiguchi T, Ito Z, Kajihara M, Misawa T, Homma S, Ohkusa T and Koido S: Inhibition of cell proliferation and growth of pancreatic cancer by silencing of carbohydrate sulfotransferase 15 in vitro and in a xenograft model. PLoS One. 10:e01429812015. View Article : Google Scholar : PubMed/NCBI
14	Verkoczy LK, Guinn Ba and Berinstein NL: Characterization of the human B cell RAG-associated gene, hBRAG, as a B cell receptor signal-enhancing glycoprotein dimer that associates with phosphorylated proteins in resting B cells. J Biol Chem. 275:20967–20979. 2000. View Article : Google Scholar : PubMed/NCBI
15	Ohtake-Niimi S, Kondo S, Ito T, Kakehi S, Ohta T, Habuchi H, Kimata K and Habuchi O: Mice deficient in N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase are unable to synthesize chondroitin/dermatan sulfate containing N-acetylgalactosamine 4,6-bissulfate residues and exhibit decreased protease activity in bone marrow-derived mast cells. J Biol Chem. 285:20793–20805. 2010. View Article : Google Scholar : PubMed/NCBI
16	Mizumoto S, Watanabe M, Yamada S and Sugahara K: Expression of N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase involved in chondroitin sulfate synthesis is responsible for pulmonary metastasis. Biomed Res Int. 2013:6563192013. View Article : Google Scholar : PubMed/NCBI
17	Sato H, Sagara S, Nakajima N, Akimoto T, Suzuki K, Yoneyama H, Terai S and Yahagi N: Prevention of esophageal stricture after endoscopic submucosal dissection using RNA-based silencing of carbohydrate sulfotransferase 15 in a porcine model. Endoscopy. 49:491–497. 2017. View Article : Google Scholar : PubMed/NCBI
18	Suzuki K, Arumugam S, Yokoyama J, Kawauchi Y, Honda Y, Sato H, Aoyagi Y, Terai S, Okazaki K, Suzuki Y, et al: Pivotal role of carbohydrate sulfotransferase 15 in fibrosis and mucosal healing in mouse colitis. PLoS One. 11:e01589672016. View Article : Google Scholar : PubMed/NCBI
19	Kai Y, Tomoda K, Yoneyama H, Kitabatake M, Nakamura A, Ito T, Yoshikawa M and Kimura H: Silencing of carbohydrate sulfotransferase 15 hinders murine pulmonary fibrosis development. Mol Ther Nucleic Acids. 6:163–172. 2017. View Article : Google Scholar : PubMed/NCBI
20	Nishimura M, Matsukawa M, Fujii Y, Matsuda Y, Arai T, Ochiai Y, Itoi T and Yahagi N: Effects of EUS-guided intratumoral injection of oligonucleotide STNM01 on tumor growth, histology, and overall survival in patients with unresectable pancreatic cancer. Gastrointest Endosc. 87:1126–1131. 2018. View Article : Google Scholar : PubMed/NCBI
21	Ito Z, Takakura K, Suka M, Kanai T, Saito R, Fujioka S, Kajihara M, Yanagisawa H, Misawa T, Akiba T, et al: Prognostic impact of carbohydrate sulfotransferase 15 in patients with pancreatic ductal adenocarcinoma. Oncol Lett. 13:4799–4805. 2017. View Article : Google Scholar : PubMed/NCBI
22	van der Steen SC, van Tilborg AA, Vallen MJ, Bulten J, van Kuppevelt TH and Massuger LF: Prognostic significance of highly sulfated chondroitin sulfates in ovarian cancer defined by the single chain antibody GD3A11. Gynecol Oncol. 140:527–536. 2016. View Article : Google Scholar : PubMed/NCBI
23	ten Dam GB, van de Westerlo EM, Purushothaman A, Stan RV, Bulten J, Sweep FC, Massuger LF, Sugahara K and van Kuppevelt TH: Antibody GD3G7 selected against embryonic glycosaminoglycans defines chondroitin sulfate-E domains highly up-regulated in ovarian cancer and involved in vascular endothelial growth factor binding. Am J Pathol. 171:1324–1333. 2007. View Article : Google Scholar : PubMed/NCBI
24	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
25	Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES and Mesirov JP: Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 102:15545–15550. 2005. View Article : Google Scholar : PubMed/NCBI
26	Liu J, Xie X, Zhou C, Peng S, Rao D and Fu J: Which factors are associated with actual 5-year survival of oesophageal squamous cell carcinoma? Eur J Cardiothorac Surg. 41:e7–e11. 2012. View Article : Google Scholar : PubMed/NCBI
27	Dedhar S: Cell-substrate interactions and signaling through ILK. Curr Opin Cell Biol. 12:250–256. 2000. View Article : Google Scholar : PubMed/NCBI
28	Hannigan G, Troussard AA and Dedhar S: Integrin-linked kinase: A cancer therapeutic target unique among its ILK. Nat Rev Cancer. 5:51–63. 2005. View Article : Google Scholar : PubMed/NCBI
29	Shirley LA, McCarty S, Yang MC, Saji M, Zhang X, Phay J, Ringel MD and Chen CS: Integrin-linked kinase affects signaling pathways and migration in thyroid cancer cells and is a potential therapeutic target. Surgery. 159:163–170. 2016. View Article : Google Scholar : PubMed/NCBI
30	Stegh AH: Targeting the p53 signaling pathway in cancer therapy-the promises, challenges and perils. Expert Opin Ther Targets. 16:67–83. 2012. View Article : Google Scholar : PubMed/NCBI
31	Hein MY, Hubner NC, Poser I, Cox J, Nagaraj N, Toyoda Y, Gak IA, Weisswange I, Mansfeld J, Buchholz F, et al: A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell. 163:712–723. 2015. View Article : Google Scholar : PubMed/NCBI
32	Montalbano J, Lui K, Sheikh MS and Huang Y: Identification and characterization of RBEL1 subfamily of GTPases in the Ras superfamily involved in cell growth regulation. J Biol Chem. 284:18129–18142. 2009. View Article : Google Scholar : PubMed/NCBI
33	Tang H, Ji F, Sun J, Xie Y, Xu Y and Yue H: RBEL1 is required for osteosarcoma cell proliferation via inhibiting retinoblastoma 1. Mol Med Rep. 13:1275–1280. 2016. View Article : Google Scholar : PubMed/NCBI
34	Hassan M, Alaoui A, Feyen O, Mirmohammadsadegh A, Essmann F, Tannapfel A, Gulbins E, Schulze-Osthoff K and Hengge UR: The BH3-only member Noxa causes apoptosis in melanoma cells by multiple pathways. Oncogene. 27:4557–4568. 2008. View Article : Google Scholar : PubMed/NCBI
35	Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, Tokino T, Taniguchi T and Tanaka N: Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science. 288:1053–1058. 2000. View Article : Google Scholar : PubMed/NCBI
36	Kumar AS, Naruszewicz I, Wang P, Leung-Hagesteijn C and Hannigan GE: ILKAP regulates ILK signaling and inhibits anchorage-independent growth. Oncogene. 23:3454–3461. 2004. View Article : Google Scholar : PubMed/NCBI
37	Leung-Hagesteijn C, Mahendra A, Naruszewicz I and Hannigan GE: Modulation of integrin signal transduction by ILKAP, a protein phosphatase 2C associating with the integrin-linked kinase, ILK1. EMBO J. 20:2160–2170. 2001. View Article : Google Scholar : PubMed/NCBI
38	Yang K, Hitomi M and Stacey DW: Variations in cyclin D1 levels through the cell cycle determine the proliferative fate of a cell. Cell Div. 1:322006. View Article : Google Scholar : PubMed/NCBI