Interaction of S100A1 with LATS1 promotes cell growth through regulation of the Hippo pathway in hepatocellular carcinoma Retraction in /10.3892/ijo.2023.5603

Guo,Qingping; Wang,Jiale; Cao,Zeyu; Tang,Yongchang; Feng,Chao; Huang,Feizhou

doi:10.3892/ijo.2018.4431

Interaction of S100A1 with LATS1 promotes cell growth through regulation of the Hippo pathway in hepatocellular carcinoma

Retraction in: /10.3892/ijo.2023.5603

Authors:
- Qingping Guo
- Jiale Wang
- Zeyu Cao
- Yongchang Tang
- Chao Feng
- Feizhou Huang
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Affiliations: Department of Hepatobiliary Surgery, The Third Xiang-Ya Hospital, Central South University, Changsha, Hunan 410013, P.R. China
Published online on: June 5, 2018 https://doi.org/10.3892/ijo.2018.4431
Pages: 592-602
Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Despite advances in surgery and chemotherapy, the prognosis of patients with hepatocellular carcinoma (HCC) remains poor. In the present study, the role of S100A1 in the progression of HCC was investigated. Immunohistochemical staining was used to measure the expression of S100A1 in HCC tissues. S100A1 was knocked down by siRNA. A battery of experiments was used to evaluate the biology functions of S100A1. It was found that S100A1 was upregulated in HCC tissues, and its upregulation was associated with a large tumor size, low differentiation and shorter survival time. The biological experiments demonstrated that S100A1 functions as an oncogene in HCC. It was also found that S100A1 knockdown enhanced the inhibitory effects of cisplatin on HCC cells. The results showed that the downregulation of S100A1 induced the phosphorylation of yes‑associated protein (YAP), and treatment with CHX demonstrated that the downregulation of S100A1 accelerated YAP protein degradation. The downregulation of S100A1 did not alter the expression of mammalian sterile 20‑like kinase (MST)1/2 or phosphorylated MST1/2, but upregulated the phosphorylation of large tumor suppressor kinase 1 (LATS1). It was further confirmed that S100A1 interacted with LATS1. LATS1 depletion significantly reduced the effects of S100A1 on cell growth rate and apoptosis, and there was a positive correlation between phosphorylated LATS1 and S100A1 in clinical samples, indicating that LATS1 was responsible for the S100A1-induced changes in cancer cell growth and Hippo signaling. In conclusion, the results of the present study indicated that S100A1 functions as an oncogene and may be a biomarker for the prognosis of patients with HCC. S100A1 exerted its oncogenic function by interacting with LATS1 and activating YAP. S100A1 may serve as a target for novel therapies in HCC.

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1	Costentin CE, Ferrone CR, Arellano RS, Ganguli S, Hong TS and Zhu AX: Hepatocellular carcinoma with macrovascular invasion: Defining the optimal treatment strategy. Liver Cancer. 6:360–374. 2017. View Article : Google Scholar
2	Liu S, Miao R, Zhai M, Pang Q, Deng Y, Liu S, Qu K, Liu C and Zhang J: Effects and related mechanisms of serotonin on malignant biological behavior of hepatocellular carcinoma via regulation of Yap. Oncotarget. 8:47412–47424. 2017.
3	Kim W, Khan SK, Liu Y, Xu R, Park O, He Y, Cha B, Gao B and Yang Y: Hepatic Hippo signaling inhibits protumoural microenvironment to suppress hepatocellular carcinoma. Gut gutjnl-2017-314061. 2017.
4	Luo X, Liu Y, Feng W, Lei L, Du Y, Wu J and Wang S: NUP37, a positive regulator of YAP/TEAD signaling, promotes the progression of hepatocellular carcinoma. Oncotarget. 8:98004–98013. 2017. View Article : Google Scholar
5	Valero V III, Pawlik TM and Anders RA: Emerging role of Hpo signaling and YAP in hepatocellular carcinoma. J Hepatocell Carcinoma. 2:69–78. 2015.
6	Wright NT, Cannon BR, Zimmer DB and Weber DJ: S100A1: Structure, function, and therapeutic potential. Curr Chem Biol. 3:138–145. 2009.
7	Rocca PC, Brunelli M, Gobbo S, Eccher A, Bragantini E, Mina MM, Ficarra V, Zattoni F, Zamò A and Pea M: Diagnostic utility of S100A1 expression in renal cell neoplasms: An immu-nohistochemical and quantitative RT-PCR study. Mod Pathol. 20:722–728. 2007. View Article : Google Scholar
8	Li G, Barthelemy A, Feng G, Gentil-Perret A, Peoc’h M, Genin C and Tostain J: S100A1: A powerful marker to differentiate chromophobe renal cell carcinoma from renal oncocytoma. Histopathology. 50:642–647. 2007. View Article : Google Scholar
9	DeRycke MS, Andersen JD, Harrington KM, Pambuccian SE, Kalloger SE, Boylan KL, Argenta PA and Skubitz AP: S100A1 expression in ovarian and endometrial endometrioid carcinomas is a prognostic indicator of relapse-free survival. Am J Clin Pathol. 132:846–856. 2009. View Article : Google Scholar
10	Tian T, Li X, Hua Z, Ma J, Liu Z, Chen H and Cui Z: S100A1 promotes cell proliferation and migration and is associated with lymph node metastasis in ovarian cancer. Discov Med. 23:235–245. 2017.
11	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Δ Δ C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar
12	Wang T, Huo X, Chong Z, Khan H, Liu R and Wang T: A review of S100 protein family in lung cancer. Clin Chim Acta. 476:54–59. 2018. View Article : Google Scholar
13	Tong L, Lan W, Lim RR and Chaurasia SS: S100A proteins as molecular targets in the ocular surface inflammatory diseases. Ocul Surf. 12:23–31. 2014. View Article : Google Scholar
14	Wang G, Rudland PS, White MR and Barraclough R: Interaction in vivo and in vitro of the metastasis-inducing S100 protein, S100A4 (9Ka) with S100A1. J Biol Chem. 275:11141–11146. 2000. View Article : Google Scholar
15	Wang G, Zhang S, Fernig DG, Martin-Fernandez M, Rudland PS and Barraclough R: Mutually antagonistic actions of S100A4 and S100A1 on normal and metastatic phenotypes. Oncogene. 24:1445–1454. 2005. View Article : Google Scholar
16	Donato R, Sorci G and Giambanco I: S100A6 protein: Functional roles. Cell Mol Life Sci. 74:2749–2760. 2017. View Article : Google Scholar
17	Fagerberg L, Hallström BM, Oksvold P, Kampf C, Djureinovic D, Odeberg J, Habuka M, Tahmasebpoor S, Danielsson A and Edlund K: Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics. 13:397–406. 2014. View Article : Google Scholar
18	Teratani T, Watanabe T, Kuwahara F, Kumagai H, Kobayashi S, Aoki U, Ishikawa A, Arai K and Nozawa R: Induced transcriptional expression of calcium-binding protein S100A1 and S100A10 genes in human renal cell carcinoma. Cancer Lett. 175:71–77. 2002. View Article : Google Scholar
19	Li G, Gentil-Perret A, Lambert C, Genin C and Tostain J: S100A1 and KIT gene expressions in common subtypes of renal tumours. Eur J Surg Oncol. 31:299–303. 2005. View Article : Google Scholar
20	Sviatoha V, Tani E, Kleina R, Sperga M and Skoog L: Immunohistochemical analysis of the S100A1, S100B, CD44 and Bcl-2 antigens and the rate of cell proliferation assessed by Ki-67 antibody in benign and malignant melanocytic tumours. Melanoma Res. 20:118–125. 2010. View Article : Google Scholar
21	Cossu-Rocca P, Contini M, Brunelli M, Festa A, Pili F, Gobbo S, Eccher A, Mura A, Massarelli G and Martignoni G: S-100A1 is a reliable marker in distinguishing nephrogenic adenoma from prostatic adenocarcinoma. Am J Surg Pathol. 33:1031–1036. 2009. View Article : Google Scholar
22	Carvalho JC, Wasco MJ, Kunju LP, Thomas DG and Shah RB: Cluster analysis of immunohistochemical profiles delineates CK7, vimentin, S100A1 and C-kit (CD117) as an optimal panel in the differential diagnosis of renal oncocytoma from its mimics. Histopathology. 58:169–179. 2011. View Article : Google Scholar
23	Kuroda N, Kanomata N, Yamaguchi T, Imamura Y, Ohe C, Sakaida N, Hes O, Michal M, Shuin T and Lee GH: Immunohistochemical application of S100A1 in renal onco-cytoma, oncocytic papillary renal cell carcinoma, and two variants of chromophobe renal cell carcinoma. Med Mol Morphol. 44:111–115. 2011. View Article : Google Scholar
24	Yordanov A, Ivanov I, Popovska S, Dineva T, Dimitrov T and Ivanova Z: Evaluation of the expression of S100A1 protein in serous, mucinous and endometroid ovarian carcinoma. Akush Ginekol (Sofiia). 52:22–26. 2013.In Bulgarian.
25	Conner JR, Hirsch MS and Jo VY: HNF1β and S100A1 are useful biomarkers for distinguishing renal oncocytoma and chro-mophobe renal cell carcinoma in FNA and core needle biopsies. Cancer Cytopathol. 123:298–305. 2015. View Article : Google Scholar
26	Hatoum D, Yagoub D, Ahadi A, Nassif NT and McGowan EM: Annexin/S100A protein family regulation through 14ARF-53 activation: A role in cell survival and predicting treatment outcomes in breast cancer. PLoS One. 12:e01699252017. View Article : Google Scholar
27	Mencía N, Selga E, Rico I, de Almagro MC, Villalobos X, Ramirez S, Adan J, Hernández JL, Noé V and Ciudad CJ: Overexpression of S100A4 in human cancer cell lines resistant to methotrexate. BMC Cancer. 10:2502010. View Article : Google Scholar
28	Tsuchiya M, Yamaguchi F, Shimamoto S, Fujimoto T, Tokumitsu H, Tokuda M and Kobayashi R: Oxidized S100A4 inhibits the activation of protein phosphatase 5 through S100A1 in MKN-45 gastric carcinoma cells. Int J Mol Med. 34:1713–1719. 2014. View Article : Google Scholar
29	Tarabykina S, Kriajevska M, Scott DJ, Hill TJ, Lafitte D, Derrick PJ, Dodson GG, Lukanidin E and Bronstein I: Heterocomplex formation between metastasis-related protein S100A4 (Mts1) and S100A1 as revealed by the yeast two-hybrid system. FEBS Lett. 475:187–191. 2000. View Article : Google Scholar
30	Watt KI, Harvey KF and Gregorevic P: Regulation of tissue growth by the mammalian Hippo signaling pathway. Front Physiol. 8:9422017. View Article : Google Scholar
31	Lin KC, Park HW and Guan KL: Regulation of the Hippo pathway transcription factor TEAD. Trends Biochem Sci. 42:862–872. 2017. View Article : Google Scholar
32	Hong AW, Meng Z and Guan KL: The Hippo pathway in intestinal regeneration and disease. Nat Rev Gastroenterol Hepatol. 13:324–337. 2016. View Article : Google Scholar
33	Yimlamai D, Fowl BH and Camargo FD: Emerging evidence on the role of the Hippo/YAP pathway in liver physiology and cancer. J Hepatol. 63:1491–1501. 2015. View Article : Google Scholar
34	Li Y, Kong F, Shao Q, Wang R, Hu E, Liu J, Jin C, He D and Xiao X: YAP expression and activity are suppressed by S100A7 via 65/NFκB-mediated repression of ΔNp63. Mol Cancer Res. 15:1752–1763. 2017. View Article : Google Scholar