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SOSTDC1 inhibits follicular thyroid cancer cell proliferation, migration, and EMT via suppressing PI3K/Akt and MAPK/Erk signaling pathways

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Abstract

The sclerostin domain containing protein 1 (SOSTDC1) is a cell signaling regulator involved in cell physiology and pathology. SOSTDC1 is known to have a suppressive effect on certain kinds of cancer. However, the role of SOSTDC1 in follicular thyroid cancer (FTC) remains unknown. We aimed to investigate if the expression of SOSTDC1 plays any roles in carcinogenesis and metastasis of FTC. We found a significantly down-regulated SOSTDC1 expression in follicular thyroid cancer samples. In addition, our data showed that ectopic expression of SOSTDC1 dramatically inhibited thyroid cancer cell proliferation in vitro and in nude mice. SOSTDC1 also compromised the migratory, invasive property, and epithelial–mesenchymal transition (EMT) activity of FTC cell. Mechanically, SOSTDC1 exerted its tumor suppressor function by inhibiting the activity of major signaling pathways including the phosphatidylinositol-3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK)/Erk pathways. Altogether, our findings provide insight into the role of SOSTDC1 as a novel functional tumor suppressor in follicular thyroid cancer through modulating the activities of PI3K/Akt and MAPK/Erk signaling pathways.

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References

  1. Schmid KW (2015) Lymph node and distant metastases of thyroid gland cancer. Metastases in the thyroid glands. Pathologe 36(2):171–175. doi:10.1007/s00292-015-0071-6

    Article  PubMed  Google Scholar 

  2. Grant CS (2015) Recurrence of papillary thyroid cancer after optimized surgery. Gland Surg 4:52–62. doi:10.3978/j.issn.2227-684X.2014.12.06

    PubMed  PubMed Central  Google Scholar 

  3. 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. doi:10.1016/j.biopha.2015.08.027

    Article  CAS  PubMed  Google Scholar 

  4. Xing M (2010) Genetic alterations in the phosphatidylinositol-3 kinase/Akt pathway in thyroid cancer. Thyroid 20:697–706. doi:10.1089/thy.2010.1646

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Marshall CJ (1995) Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell 80:179–185

    Article  CAS  PubMed  Google Scholar 

  6. Jia S, Lu J, Qu T, Feng Y, Wang X, Liu C, Ji J (2017) MAGI1 inhibits migration and invasion via blocking MAPK/ERK signaling pathway in gastric cancer. Chin J Cancer Res 29:25–35. doi:10.21147/j.issn.1000-9604.2017.01.04

    Article  PubMed  PubMed Central  Google Scholar 

  7. Nguyen A, Moussallieh FM, Mackay A, Cicek AE, Coca A, Pierre Chenard M, Weingertner N, Lhermitte B, Letouze E, Guerin E, Pencreach E, Jannier S, Guenot D, Jacques Namer I, Jones C, Entz-Werle N (2017) Characterization of the transcriptional and metabolic responses of pediatric high grade gliomas to mTOR-HIF-1a axis inhibition. Oncotarget. doi:10.18632/oncotarget.16500

    Google Scholar 

  8. Nikiforov YE, Nikiforova MN (2011) Molecular genetics and diagnosis of thyroid cancer. Nat Rev Endocrinol 7:569–580. doi:10.1038/nrendo.2011.142

    Article  CAS  PubMed  Google Scholar 

  9. Ren L, Hong ES, Mendoza A, Issaq S, Tran Hoang C, Lizardo M, LeBlanc A, Khanna C (2017) Metabolomics uncovers a link between inositol metabolism and osteosarcoma metastasis. Oncotarget. doi:10.18632/oncotarget.15872

    Google Scholar 

  10. Larue L, Bellacosa A (2005) Epithelial-mesenchymal transition in development and cancer: role of phosphatidylinositol 3′ kinase/AKT pathways. Oncogene 24:7443–7454. doi:10.1038/sj.onc.1209091

    Article  CAS  PubMed  Google Scholar 

  11. Iwatsuki M, Mimori K, Yokobori T, Ishi H, Beppu T, Nakamori S, Baba H, Mori M (2010) Epithelial-mesenchymal transition in cancer development and its clinical significance. Cancer Sci 101:293–299. doi:10.1111/j.1349-7006.2009.01419.x

    Article  CAS  PubMed  Google Scholar 

  12. Laurikkala J, Kassai Y, Pakkasjarvi L, Thesleff I, Itoh N (2003) Identification of a secreted BMP antagonist, ectodin, integrating BMP, FGF, and SHH signals from the tooth enamel knot. Dev Biol 264:91–105

    Article  CAS  PubMed  Google Scholar 

  13. Liu L, Wu S, Yang Y, Cai J, Zhu X, Wu J, Li M, Guan H (2016) SOSTDC1 is down-regulated in non-small cell lung cancer and contributes to cancer cell proliferation. Cell Biosci 6:24. doi:10.1186/s13578-016-0091-9

    Article  PubMed  PubMed Central  Google Scholar 

  14. Gopal G, Raja UM, Shirley S, Rajalekshmi KR, Rajkumar T (2013) SOSTDC1 down-regulation of expression involves CpG methylation and is a potential prognostic marker in gastric cancer. Cancer Genet 206:174–182. doi:10.1016/j.cancergen.2013.04.005

    Article  CAS  PubMed  Google Scholar 

  15. Lan L, Basourakos S, Cui D, Zuo X, Deng W, Huo L, Chen L, Zhang G, Deng L, Shi B, Luo Y (2017) Inhibiting beta-catenin expression promotes efficiency of radioiodine treatment in aggressive follicular thyroid cancer cells probably through mediating NIS localization. Oncol Rep 37:426–434. doi:10.3892/or.2016.5228

    Article  PubMed  Google Scholar 

  16. Xu XC, Abuduhadeer X, Zhang WB, Li T, Gao H, Wang YH (2013) Knockdown of RAGE inhibits growth and invasion of gastric cancer cells. Eur J Histochem 57:e36. doi:10.4081/ejh.2013.e36

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kim KR, Park KK, Chung WY, Hwang YS (2013) The inhibitory effect of buddlejasaponin IV on the growth of YD-10B human oral squamous cell carcinoma cells. J Cancer Prev 18:330–336

    Article  PubMed  PubMed Central  Google Scholar 

  18. Im CN, Kim BM, Moon EY, Hong DW, Park JW, Hong SH (2013) Characterization of H460R, a radioresistant human lung cancer cell line, and involvement of syntrophin beta 2 (SNTB2) in radioresistance. Genomics Inform 11:245–253. doi:10.5808/gi.2013.11.4.245

    Article  PubMed  PubMed Central  Google Scholar 

  19. Gao FL, Li WS, Liu CL, Zhao GQ (2013) Silencing Bmi-1 enhances the senescence and decreases the metastasis of human gastric cancer cells. World J Gastroenterol 19:8764–8769. doi:10.3748/wjg.v19.i46.8764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Tesfay L, Clausen KA, Kim JW, Hegde P, Wang X, Miller LD, Deng Z, Blanchette N, Arvedson T, Miranti CK, Babitt JL, Lin HY, Peehl DM, Torti FM, Torti SV (2015) Hepcidin regulation in prostate and its disruption in prostate cancer. Cancer Res 75:2254–2263. doi:10.1158/0008-5472.can-14-2465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Krepischi AC, Maschietto M, Ferreira EN, Silva AG, Costa SS, da Cunha IW, Barros BD, Grundy PE, Rosenberg C, Carraro DM (2016) Genomic imbalances pinpoint potential oncogenes and tumor suppressors in wilms tumors. Mol Cytogenet 9:20. doi:10.1186/s13039-016-0227-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Altomare DA, Testa JR (2005) Perturbations of the AKT signaling pathway in human cancer. Oncogene 24:7455–7464

    Article  CAS  PubMed  Google Scholar 

  23. Nicholson KM, Anderson NG (2002) The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal 14:381–395

    Article  CAS  PubMed  Google Scholar 

  24. Xue G, Hemmings BA (2013) PKB/Akt-dependent regulation of cell motility. J Natl Cancer Inst 105:393–404. doi:10.1093/jnci/djs648

    Article  CAS  PubMed  Google Scholar 

  25. Altomare DA, Testa JR (2005) Perturbations of the AKT signaling pathway in human cancer. Oncogene 24:7455–7464. doi:10.1038/sj.onc.1209085

    Article  CAS  PubMed  Google Scholar 

  26. Carnero A, Blanco-Aparicio C, Renner O, Link W, Leal JF (2008) The PTEN/PI3K/AKT signalling pathway in cancer, therapeutic implications. Curr Cancer Drug Targets 8:187–198

    Article  CAS  PubMed  Google Scholar 

  27. Kim EK, Choi EJ (2010) Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta 1802:396–405. doi:10.1016/j.bbadis.2009.12.009

    Article  CAS  PubMed  Google Scholar 

  28. Henley KD, Gooding KA, Economides AN, Gannon M (2012) Inactivation of the dual Bmp/Wnt inhibitor Sostdc1 enhances pancreatic islet function. Am J Physiol Endocrinol Metab 303:E752–E761. doi:10.1152/ajpendo.00531.2011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Al-Hussaini H, Kilarkaje N, Shahabi G, Al-Mulla F (2016) Proliferation and migration of peripheral retinal pigment epithelial cells are associated with the upregulation of wingless-related integration and bone morphogenetic protein signaling in dark agouti rats. Med Princ Pract 25:408–416. doi:10.1159/000446480

    Article  PubMed  Google Scholar 

  30. Brooker SM, Gobeske KT, Chen J, Peng CY, Kessler JA (2016) Hippocampal bone morphogenetic protein signaling mediates behavioral effects of antidepressant treatment. Mol Psychiatry. doi:10.1038/mp.2016.160

    PubMed  PubMed Central  Google Scholar 

  31. Hover LD, Owens P, Munden AL, Wang J, Chambless LB, Hopkins CR, Hong CC, Moses HL, Abel TW (2016) Bone morphogenetic protein signaling promotes tumorigenesis in a murine model of high-grade glioma. Neuro Oncol 18:928–938. doi:10.1093/neuonc/nov310

    Article  PubMed  Google Scholar 

  32. Li H, Zhao D, Wang S, Ding J, Zhao L (2016) Bone morphogenetic protein9 promotes the differentiation of mouse spleen macrophages into osteoclasts via the ALK1 receptor and ERK 1/2 pathways in vitro. Mol Med Rep 14:4545–4550. doi:10.3892/mmr.2016.5803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Chiba T, Ishisaki A, Kyakumoto S, Shibata T, Yamada H, Kamo M (2016) Transforming growth factor-beta1 suppresses bone morphogenetic protein-2-induced mesenchymal-epithelial transition in HSC-4 human oral squamous cell carcinoma cells via Smad1/5/9 pathway suppression. Oncol Rep. doi:10.3892/or.2016.5338

    PubMed Central  Google Scholar 

  34. Tan CC, Li GX, Tan LD, Du X, Li XQ, He R, Wang QS, Feng YM (2016) Breast cancer cells obtain an osteomimetic feature via epithelial-mesenchymal transition that have undergone BMP2/RUNX2 signaling pathway induction. Oncotarget 7:79688–79705. doi:10.18632/oncotarget.12939

    PubMed  PubMed Central  Google Scholar 

  35. Zhang L, Ye Y, Long X, Xiao P, Ren X, Yu J (2016) BMP signaling and its paradoxical effects in tumorigenesis and dissemination. Oncotarget 7:78206–78218. doi:10.18632/oncotarget.12151

    PubMed  PubMed Central  Google Scholar 

  36. Yeung KT, Yang J (2017) Epithelial-mesenchymal transition in tumor metastasis. Mol Oncol 11:28–39. doi:10.1002/1878-0261.12017

    Article  PubMed  Google Scholar 

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Author notes

  1. Qinyi Zhou and Jun Chen have been contributed equally to this work and should be considered as equal first coauthors.

Authors and Affiliations

  1. Department of Head and Neck Surgery, RenJi Hospital, School of Medicine, Shanghai Jiao Tong University, #145 Shandongzhong Road, Huangpu District, Shanghai, 200001, China

    Qinyi Zhou, Jun Chen, Jialin Feng, Yanan Xu, Wenjie Zheng & Jiadong Wang

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  1. Qinyi Zhou
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  2. Jun Chen
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  3. Jialin Feng
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  4. Yanan Xu
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  5. Wenjie Zheng
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  6. Jiadong Wang
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Correspondence to Jiadong Wang.

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Zhou, Q., Chen, J., Feng, J. et al. SOSTDC1 inhibits follicular thyroid cancer cell proliferation, migration, and EMT via suppressing PI3K/Akt and MAPK/Erk signaling pathways. Mol Cell Biochem 435, 87–95 (2017). https://doi.org/10.1007/s11010-017-3059-0

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