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Periostin silencing suppresses the aggressive phenotype of thyroid carcinoma cells by suppressing the Akt/thyroid stimulating hormone receptor axis

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Abstract

Clinical evidence indicates that high periostin expression correlates with aggressive phenotype in thyroid carcinoma. However, the biological roles of periostin in thyroid carcinoma development and progression are still unclear. In this study, we explored the effects of periostin silencing on thyroid carcinoma cell growth, invasion, and tumorigenesis. We also studied the impact of periostin on the activation of phosphoinositide 3-kinase (PI3-K)/Akt signaling, which is involved in the pathogenesis of thyroid carcinoma. It was found that downregulation of periostin significantly inhibited the proliferation, colony formation, and invasion in both FTC-133 and BCPAP thyroid carcinoma cells. In vivo tumorigenic studies confirmed that periostin depletion retarded the growth of subcutaneous FTC-133 xenograft tumors, which was coupled with a significant decline in the percentage of Ki-67-positive proliferating cells. Western blot analysis demonstrated that periostin downregulation caused a marked inhibition of thyroid stimulating hormone receptor (TSHR) expression and Akt phosphorylation in FTC-133 and BCPAP cells. Co-expression of constitutively active Akt (CA-Akt) significantly reversed periostin-mediated downregulation of TSHR. Most importantly, overexpression of TSHR or CA-Akt rescued FTC-133 cells from periostin-induced growth and invasion suppression. Collectively, periostin regulates thyroid carcinoma growth and progression via the Akt/TSHR axis and represents a promising therapeutic target for this malignancy.

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References

  • Bai Y, Kakudo K, Nakamura M, Ozaki T, Li Y, Liu Z, Mori I, Miyauchi A, Zhou G (2009) Loss of cellular polarity/cohesiveness in the invasive front of papillary thyroid carcinoma and periostin expression. Cancer Lett 281:188–195

    Article  CAS  Google Scholar 

  • Cha YJ, Koo JS (2016) Next-generation sequencing in thyroid cancer. J Trans Med 14:322

    Article  Google Scholar 

  • Davies TF, Yin X, Latif R (2010) The genetics of the thyroid stimulating hormone receptor: history and relevance. Thyroid 20:727–736

    Article  CAS  Google Scholar 

  • Eng OS, Grant SB, Weissler J, Simon M, Roychowdhury S, Davidov T, Trooskin SZ (2016) Operative bed recurrence of thyroid cancer: utility of a preoperative needle localization technique. Gland Surg 5:571–575

    Article  Google Scholar 

  • Hong S, Yu S, Li J, Yin Y, Liu Y, Zhang Q, Guan H, Li Y, Xiao H (2016) MiR-20b displays tumor-suppressor functions in papillary thyroid carcinoma by regulating the MAPK/ERK signaling pathway. Thyroid 26:1733–1743

    Article  CAS  Google Scholar 

  • Ishiba T, Nagahara M, Nakagawa T, Sato T, Ishikawa T, Uetake H, Sugihara K, Miki Y, Nakanishi A (2014) Periostin suppression induces decorin secretion leading to reduced breast cancer cell motility and invasion. Sci Rep 4:7069

    Article  Google Scholar 

  • Kleinau G, Worth CL, Kreuchwig A, Biebermann H, Marcinkowski P, Scheerer P, Krause G (2017) Structural-functional features of the thyrotropin receptor: a class A G-protein-coupled receptor at work. Front Endocrinol (Lausanne) 8:86

    Article  Google Scholar 

  • Kohn AD, Takeuchi F, Roth RA (1996) Akt, a pleckstrin homology domain containing kinase, is activated primarily by phosphorylation. J Biol Chem 271:21920–21926

    Article  CAS  Google Scholar 

  • Landré V, Antonov A, Knight R, Melino G (2016) p73 promotes glioblastoma cell invasion by directly activating POSTN (periostin) expression. Oncotarget 7:11785–11802

    Article  Google Scholar 

  • Lim ST, Jeon YW, Suh YJ (2016) The prognostic values of preoperative tumor volume and tumor diameter in T1N0 papillary thyroid cancer. Cancer Res Treat. doi:10.4143/crt.2016.325

    Google Scholar 

  • Mainetti LE, Rico MJ, Fernández-Zenobi MV, Perroud HA, Roggero EA, Rozados VR, Scharovsky OG (2013) Therapeutic efficacy of metronomic chemotherapy with cyclophosphamide and doxorubicin on murine mammary adenocarcinomas. Ann Oncol 24:2310–2316

    Article  CAS  Google Scholar 

  • Miao X, Jia L, Zhou H, Song X, Zhou M, Xu J, Zhao L, Feng X, Zhao Y (2016) miR-4299 mediates the invasive properties and tumorigenicity of human follicular thyroid carcinoma by targeting ST6GALNAC4. IUBMB Life 68:136–144

    Article  CAS  Google Scholar 

  • Naik PK, Bozyk PD, Bentley JK, Popova AP, Birch CM, Wilke CA, Fry CD, White ES, Sisson TH, Tayob N, Carnemolla B, Orecchia P, Flaherty KR, Hershenson MB, Murray S, Martinez FJ, Moore BB, COMET Investigators (2012) Periostin promotes fibrosis and predicts progression in patients with idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 303:L1046–L1056

    Article  CAS  Google Scholar 

  • Nozhat Z, Hedayati M (2016) PI3 K/AKT pathway and its mediators in thyroid carcinomas. Mol Diagn Ther 20:13–26

    Article  CAS  Google Scholar 

  • Nuzzo PV, Rubagotti A, Zinoli L, Salvi S, Boccardo S, Boccardo F (2016) The prognostic value of stromal and epithelial periostin expression in human breast cancer: correlation with clinical pathological features and mortality outcome. BMC Cancer 16:95

    Article  CAS  Google Scholar 

  • Patel PN, Yu XM, Jaskula-Sztul R, Chen H (2014) Hesperetin activates the Notch1 signaling cascade, causes apoptosis, and induces cellular differentiation in anaplastic thyroid cancer. Ann Surg Oncol 21:S497–S504

    Article  Google Scholar 

  • Puppin C, Fabbro D, Dima M, Di Loreto C, Puxeddu E, Filetti S, Russo D, Damante G (2008) High periostin expression correlates with aggressiveness in papillary thyroid carcinomas. J Endocrinol 197:401–408

    Article  CAS  Google Scholar 

  • Qin X, Yan M, Zhang J, Wang X, Shen Z, Lv Z, Li Z, Wei W, Chen W (2016) TGFβ3-mediated induction of periostin facilitates head and neck cancer growth and is associated with metastasis. Sci Rep 6:20587

    Article  CAS  Google Scholar 

  • Rowe CW, Paul JW, Gedye C, Tolosa JM, Bendinelli C, McGrath S, Smith R (2017) Targeting the TSH receptor in thyroid cancer. Endocr Relat Cancer 24:R191–R202

    Article  Google Scholar 

  • Shirley LA, McCarty S, Yang MC, Saji M, Zhang X, Phay J, Ringel MD, Chen CS (2016) Integrin-linked kinase affects signaling pathways and migration in thyroid cancer cells and is a potential therapeutic target. Surgery 159:163–170

    Article  Google Scholar 

  • Silvers CR, Liu YR, Wu CH, Miyamoto H, Messing EM, Lee YF (2016) Identification of extracellular vesicle-borne periostin as a feature of muscle-invasive bladder cancer. Oncotarget 7:23335–23345

    Article  Google Scholar 

  • Wang SC, Chai DS, Chen CB, Wang ZY, Wang L (2015) HPIP promotes thyroid cancer cell growth, migration and EMT through activating PI3 K/AKT signaling pathway. Biomed Pharmacother 75:33–39

    Article  CAS  Google Scholar 

  • Xiao ZM, Wang XY, Wang AM (2015) Periostin induces chemoresistance in colon cancer cells through activation of the PI3 K/Akt/survivin pathway. Biotechnol Appl Biochem 62:401–406

    Article  CAS  Google Scholar 

  • Xie X, Shi X, Guan H, Guo Q, Fan C, Dong W, Wang G, Li F, Shan Z, Cao L, Teng W (2017) P21-activated kinase 4 involves TSH induced papillary thyroid cancer cell proliferation. Oncotarget 8:24882–24891

    Google Scholar 

  • Xu X, Zheng Q, Zhang Z, Zhang X, Liu R, Liu P (2015) Periostin enhances migration, invasion, and adhesion of human endometrial stromal cells through integrin-linked kinase 1/Akt signaling pathway. Reprod Sci 22:1098–1106

    Article  CAS  Google Scholar 

  • Xu X, Chang W, Yuan J, Han X, Tan X, Ding Y, Luo Y, Cai H, Liu Y, Gao X, Liu Q, Yu Y, Du Y, Wang H, Ma L, Wang J, Chen K, Ding Y, Fu C, Cao G (2016) Periostin expression in intra-tumoral stromal cells is prognostic and predictive for colorectal carcinoma via creating a cancer-supportive niche. Oncotarget 7:798–813

    Google Scholar 

  • Zheng H, Wang M, Jiang L, Chu H, Hu J, Ning J, Li B, Wang D, Xu J (2016) BRAF-activated long noncoding RNA modulates papillary thyroid carcinoma cell proliferation through regulating thyroid stimulating hormone receptor. Cancer Res Treat 48:698–707

    Article  CAS  Google Scholar 

  • Zhong Z, Hu Z, Jiang Y, Sun R, Chen X, Chu H, Zeng M, Sun C (2016) Interleukin-11 promotes epithelial-mesenchymal transition in anaplastic thyroid carcinoma cells through PI3 K/Akt/GSK3β signaling pathway activation. Oncotarget 7:59652–59663

    Google Scholar 

  • Zhou W, Ke SQ, Huang Z, Flavahan W, Fang X, Paul J, Wu L, Sloan AE, McLendon RE, Li X, Rich JN, Bao S (2015) Periostin secreted by glioblastoma stem cells recruits M2 tumour-associated macrophages and promotes malignant growth. Nat Cell Biol 17:170–182

    Article  CAS  Google Scholar 

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Correspondence to Zhihai Peng.

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Wang, M., Gui, C., Qiu, S. et al. Periostin silencing suppresses the aggressive phenotype of thyroid carcinoma cells by suppressing the Akt/thyroid stimulating hormone receptor axis. Cytotechnology 70, 275–284 (2018). https://doi.org/10.1007/s10616-017-0141-0

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  • DOI: https://doi.org/10.1007/s10616-017-0141-0

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