S100A16 suppresses the proliferation, migration and invasion of colorectal cancer cells in part via the JNK/p38 MAPK pathway

Ou,Shiyu; Liao,Yan; Shi,Jie; Tang,Jing; Ye,Yanqing; Wu,Fengfei; Wang,Weidong; Fei,Jieying; Xie,Fang; Bai,Lan

doi:10.3892/mmr.2020.11803

S100A16 suppresses the proliferation, migration and invasion of colorectal cancer cells in part via the JNK/p38 MAPK pathway

Authors:
- Shiyu Ou
- Yan Liao
- Jie Shi
- Jing Tang
- Yanqing Ye
- Fengfei Wu
- Weidong Wang
- Jieying Fei
- Fang Xie
- Lan Bai
View Affiliations

Affiliations: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
Published online on: December 22, 2020 https://doi.org/10.3892/mmr.2020.11803
Article Number: 164
Copyright: © Ou 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

S100 calcium binding protein A16 (S100A16) is the most recent member of the S100 calcium-binding protein family. The function of S100A16 has been associated with various types of cancer; however, its role in colorectal cancer (CRC) remains unknown. Therefore, the aim of the present study was to investigate the role of S100A16 in CRC progression. The Oncomine dataset used in the current study revealed that the expression of S100A16 was decreased in CRC compared with normal colorectal tissues. Similar results were also determined via immunohistochemistry. In addition, a negative association was identified between S100A16 expression and the prognosis of patients with CRC. Further functional experiments revealed that S100A16 knockdown promoted the proliferation, migration and invasion of HCT116 and SW480 cells, and vice versa in Lovo cells. Epithelial-mesenchymal transition (EMT) was promoted and the JNK/p38 MAPK pathway was activated in HCT116 cells following S100A16 knockdown, as determined via western blotting. Furthermore, S100A16 silencing promoted the migration and invasion of cells. EMT was also reversed when cells were treated with the JNK inhibitor (SP600125) or the p38 inhibitor (SB203580). In summary, the results of the present study demonstrated that S100A16 suppressed the proliferation, migration and invasion of CRC cells partially via the JNK/p38 MAPK signalling pathway and subsequent EMT mediation.

View Figures

View References

1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2019. CA Cancer J Clin. 69:7–34. 2019. View Article : Google Scholar : PubMed/NCBI
2	Gupta GP and Massagué J: Cancer metastasis: Building a framework. Cell. 127:679–695. 2006. View Article : Google Scholar : PubMed/NCBI
3	Keane MG and Johnson GJ: Early diagnosis improves survival in colorectal cancer. Practitioner. 256:15–18, 2. 2012.PubMed/NCBI
4	Sturchler E, Cox JA, Durussel I, Weibel M and Heizmann CW: S100A16, a novel calcium-binding protein of the EF-hand superfamily. J Biol Chem. 281:38905–38917. 2006. View Article : Google Scholar : PubMed/NCBI
5	Donato R: S100: A multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles. Int J Biochem Cell Biol. 33:637–668. 2001. View Article : Google Scholar : PubMed/NCBI
6	Sedaghat F and Notopoulos A: S100 protein family and its application in clinical practice. Hippokratia. 12:198–204. 2008.PubMed/NCBI
7	Heizmann CW: The multifunctional S100 protein family. Methods Mol Biol. 172:69–80. 2002.PubMed/NCBI
8	Domínguez B, Pardo BG, Noia M, Millán A, Gómez-Tato A, Martínez P, Leiro J and Lamas J: Microarray analysis of the inflammatory and immune responses in head kidney turbot leucocytes treated with resveratrol. Int Immunopharmacol. 15:588–596. 2013. View Article : Google Scholar : PubMed/NCBI
9	Li D, Zhang R, Zhu W, Xue Y, Zhang Y, Huang Q, Liu M and Liu Y: S100A16 inhibits osteogenesis but stimulates adipogenesis. Mol Biol Rep. 40:3465–3473. 2013. View Article : Google Scholar : PubMed/NCBI
10	Babini E, Bertini I, Borsi V, Calderone V, Hu X, Luchinat C and Parigi G: Structural characterization of human S100A16, a low-affinity calcium binder. J Biol Inorg Chem. 16:243–256. 2011. View Article : Google Scholar : PubMed/NCBI
11	Wang C, Zhu X, Li A, Yang S, Qiao R and Zhang J: S100A16 regulated by Snail promotes the chemoresistance of nonmuscle invasive bladder cancer through the AKT/Bcl-2 pathway. Cancer Manag Res. 11:2449–2456. 2019. View Article : Google Scholar : PubMed/NCBI
12	Chen, Luo L and Liang C: Aberrant S100A16 expression might be an independent prognostic indicator of unfavorable survival in non-small cell lung adenocarcinoma. PLoS One. 13:e1974022018.
13	Zhou W, Pan H, Xia T, Xue J, Cheng L, Fan P, Zhang Y, Zhu W, Xue Y, Liu X, et al: Up-regulation of S100A16 expression promotes epithelial-mesenchymal transition via Notch1 pathway in breast cancer. J Biomed Sci. 21:972014. View Article : Google Scholar : PubMed/NCBI
14	Sapkota D, Bruland O, Parajuli H, Osman TA, Teh MT, Johannessen AC and Costea DE: S100A16 promotes differentiation and contributes to a less aggressive tumor phenotype in oral squamous cell carcinoma. BMC Cancer. 15:6312015. View Article : Google Scholar : PubMed/NCBI
15	Sun X, Wang T, Zhang C, Ning K, Guan ZR, Chen SX, Hong TT and Hua D: S100A16 is a prognostic marker for colorectal cancer. J Surg Oncol. 117:275–283. 2018. View Article : Google Scholar : PubMed/NCBI
16	Skrzypczak M, Goryca K, Rubel T, Paziewska A, Mikula M, Jarosz D, Pachlewski J, Oledzki J and Ostrowski J: Modeling oncogenic signaling in colon tumors by multidirectional analyses of microarray data directed for maximization of analytical reliability. PLoS One. 5:52010. View Article : Google Scholar
17	Shi J, Sun S, Liao Y, Tang J, Xu X, Qin B, Qin C, Peng L, Luo M, Bai L, et al: Advanced oxidation protein products induce G1 phase arrest in intestinal epithelial cells via a RAGE/CD36-JNK-p27kip1 mediated pathway. Redox Biol. 25:1011962019. View Article : Google Scholar : PubMed/NCBI
18	Tang J, Liao Y, He S, Shi J, Peng L, Xu X, Xie F, Diao N, Huang J, Xie Q, et al: Autocrine parathyroid hormone-like hormone promotes intrahepatic cholangiocarcinoma cell proliferation via increased ERK/JNK-ATF2-cyclinD1 signaling. J Transl Med. 15:2382017. View Article : Google Scholar : PubMed/NCBI
19	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
20	Zhu W, Xue Y, Liang C, Zhang R, Zhang Z, Li H, Su D, Liang X, Zhang Y, Huang Q, et al: S100A16 promotes cell proliferation and metastasis via AKT and ERK cell signaling pathways in human prostate cancer. Tumour Biol. 37:12241–12250. 2016. View Article : Google Scholar : PubMed/NCBI
21	Yang MH, Zhao L, Wang L, Ou-Yang W, Hu SS, Li WL, Ai ML, Wang YQ, Han Y, Li TT, et al: Nuclear lncRNA HOXD-AS1 suppresses colorectal carcinoma growth and metastasis via inhibiting HOXD3-induced integrin β3 transcriptional activating and MAPK/AKT signalling. Mol Cancer. 18:312019. View Article : Google Scholar : PubMed/NCBI
22	Schroyer AL, Stimes NW, Abi Saab WF and Chadee DN: MLK3 phosphorylation by ERK1/2 is required for oxidative stress-induced invasion of colorectal cancer cells. Oncogene. 37:1031–1040. 2018. View Article : Google Scholar : PubMed/NCBI
23	Marenholz I and Heizmann CW: S100A16, a ubiquitously expressed EF-hand protein which is up-regulated in tumors. Biochem Biophys Res Commun. 313:237–244. 2004. View Article : Google Scholar : PubMed/NCBI
24	Duan L, Wu R, Zou Z, Wang H, Ye L, Li H, Yuan S, Li X, Zha H, Sun H, et al: S100A6 stimulates proliferation and migration of colorectal carcinoma cells through activation of the MAPK pathways. Int J Oncol. 44:781–790. 2014. View Article : Google Scholar : PubMed/NCBI
25	Niu Y, Shao Z, Wang H, Yang J, Zhang F, Luo Y, Xu L, Ding Y and Zhao L: LASP1-S100A11 axis promotes colorectal cancer aggressiveness by modulating TGFβ/Smad signaling. Sci Rep. 6:261122016. View Article : Google Scholar : PubMed/NCBI
26	Masuda T, Ishikawa T, Mogushi K, Okazaki S, Ishiguro M, Iida S, Mizushima H, Tanaka H, Uetake H and Sugihara K: Overexpression of the S100A2 protein as a prognostic marker for patients with stage II and III colorectal cancer. Int J Oncol. 48:975–982. 2016. View Article : Google Scholar : PubMed/NCBI
27	Liu B, Sun WY, Zhi CY, Lu TC, Gao HM, Zhou JH, Yan WQ and Gao HC: Role of S100A3 in human colorectal cancer and the anticancer effect of cantharidinate. Exp Ther Med. 6:1499–1503. 2013. View Article : Google Scholar : PubMed/NCBI
28	Dahlmann M, Okhrimenko A, Marcinkowski P, Osterland M, Herrmann P, Smith J, Heizmann CW, Schlag PM and Stein U: RAGE mediates S100A4-induced cell motility via MAPK/ERK and hypoxia signaling and is a prognostic biomarker for human colorectal cancer metastasis. Oncotarget. 5:3220–3233. 2014. View Article : Google Scholar : PubMed/NCBI
29	Zha H, Sun H, Li X, Duan L, Li A, Gu Y, Zeng Z, Zhao J, Xie J, Yuan S, et al: S100A8 facilitates the migration of colorectal cancer cells through regulating macrophages in the inflammatory microenvironment. Oncol Rep. 36:279–290. 2016. View Article : Google Scholar : PubMed/NCBI
30	Wang HY, Zhang JY, Cui JT, Tan XH, Li WM, Gu J and Lu YY: Expression status of S100A14 and S100A4 correlates with metastatic potential and clinical outcome in colorectal cancer after surgery. Oncol Rep. 23:45–52. 2010.PubMed/NCBI
31	Sapkota D, Costea DE, Ibrahim SO, Johannessen AC and Bruland O: S100A14 interacts with S100A16 and regulates its expression in human cancer cells. PLoS One. 8:e760582013. View Article : Google Scholar : PubMed/NCBI
32	Kobayashi M, Nagashio R, Saito K, Aguilar-Bonavides C, Ryuge S, Katono K, Igawa S, Tsuchiya B, Jiang SX, Ichinoe M, et al: Prognostic significance of S100A16 subcellular localization in lung adenocarcinoma. Hum Pathol. 74:148–155. 2018. View Article : Google Scholar : PubMed/NCBI
33	Brabletz T, Kalluri R, Nieto MA and Weinberg RA: EMT in cancer. Nat Rev Cancer. 18:128–134. 2018. View Article : Google Scholar : PubMed/NCBI
34	Zeindl-Eberhart E, Brandl L, Liebmann S, Ormanns S, Scheel SK, Brabletz T, Kirchner T and Jung A: Epithelial-mesenchymal transition induces endoplasmic-reticulum-stress response in human colorectal tumor cells. PLoS One. 9:e873862014. View Article : Google Scholar : PubMed/NCBI
35	Tanaka M, Ichikawa-Tomikawa N, Shishito N, Nishiura K, Miura T, Hozumi A, Chiba H, Yoshida S, Ohtake T and Sugino T: Co-expression of S100A14 and S100A16 correlates with a poor prognosis in human breast cancer and promotes cancer cell invasion. BMC Cancer. 15:532015. View Article : Google Scholar : PubMed/NCBI