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C6orf106 accelerates pancreatic cancer cell invasion and proliferation via activating ERK signaling pathway

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Abstract

C6orf106 was highly expressed in lung and breast cancer, and proposed as clinicopathologic factor for the development of those types of cancer. However, its expression in pancreatic cancer and the mechanism that C6orf106 functions as an oncogene has not been confirmed. In the present study, we found that C6orf106 was also up-regulated in pancreatic cancer tissues and cell lines. Furthermore, C6orf106 expression was associated with advanced T stage (P = 0.010), positive regional lymph node metastasis (P = 0.012), and advanced TNM stage (P = 0.006). In vitro experiments also showed that C6orf106 served a tumor enhancer in pancreatic cancer, through increasing the expression of Snail, Cyclin D1 and Cyclin E1, and reducing the expression of E-cadherin via activating extracellular-signal-regulated kinase (ERK)- p90-kDa ribosomal S6 kinases (P90RSK) signaling pathway. The addition of ERK inhibitor PD98059 counteracted the upregulation of Snail, Cyclin D1 and Cyclin E1, and restored the expression of E-cadherin, which indicated that C6orf106 was an upstream factor of ERK signaling pathway. Taken together, the present study indicates that C6orf106 facilitates invasion and proliferation of pancreatic cancer cells, likely via activating ERK-P90RSK signaling pathway.

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References

  1. Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM (2014) Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 74(11):2913–2921. https://doi.org/10.1158/0008-5472.CAN-14-0155

    Article  CAS  PubMed  Google Scholar 

  2. Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA 68(1):7–30. https://doi.org/10.3322/caac.21442

    Article  PubMed  Google Scholar 

  3. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2013) GLOBOCAN 2012 v1.1, Cancer incidence and mortality worldwide: IARC CancerBase No. 11. Inernational Agency for Research on Cancer [accessed on October 28, 2014]. http://globocan.Iarc.Fr

  4. He XY, Yuan YZ (2014) Advances in pancreatic cancer research: moving towards early detection. World J Gastroenterol 20(32):11241–11248. https://doi.org/10.3748/wjg.v20.i32.11241

    Article  PubMed  PubMed Central  Google Scholar 

  5. Bardeesy N, DePinho RA (2002) Pancreatic cancer biology and genetics. Nat Rev Cancer 2(12):897–909. https://doi.org/10.1038/nrc949

    Article  CAS  PubMed  Google Scholar 

  6. Hidalgo M (2010) Pancreatic cancer. N Engl J Med 362(17):1605–1617. https://doi.org/10.1056/NEJMra0901557

    Article  CAS  PubMed  Google Scholar 

  7. Lillemoe KD, Yeo CJ, Cameron JL (2000) Pancreatic cancer: state-of-the-art care. CA 50(4):241–268

    CAS  PubMed  Google Scholar 

  8. Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA 66(1):7–30. https://doi.org/10.3322/caac.21332

    Article  PubMed  Google Scholar 

  9. Zhang X, Miao Y, Yu X, Zhang Y, Jiang G, Liu Y, Yu J, Han Q, Zhao H, Wang E (2015) C6orf106 enhances NSCLC cell invasion by upregulating vimentin, and downregulating E-cadherin and P120ctn. Tumour Biol 36(8):5979–5985. https://doi.org/10.1007/s13277-015-3274-9

    Article  CAS  PubMed  Google Scholar 

  10. Jiang G, Zhang X, Zhang Y, Wang L, Fan C, Xu H, Miao Y, Wang E (2015) A novel biomarker C6orf106 promotes the malignant progression of breast cancer. Tumour Biol 36(10):7881–7889. https://doi.org/10.1007/s13277-015-3500-5

    Article  CAS  PubMed  Google Scholar 

  11. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  Google Scholar 

  12. Karicheva O, Rodriguez-Vargas JM, Wadier N, Martin-Hernandez K, Vauchelles R, Magroun N, Tissier A, Schreiber V, Dantzer F (2016) PARP3 controls TGFbeta and ROS driven epithelial-to-mesenchymal transition and stemness by stimulating a TG2-Snail-E-cadherin axis. Oncotarget 7(39):64109–64123. https://doi.org/10.18632/oncotarget.11627

    Article  PubMed  PubMed Central  Google Scholar 

  13. Bai L, Yu Z, Zhang J, Yuan S, Liao C, Jeyabal PV, Rubio V, Chen H, Li Y, Shi ZZ (2016) OLA1 contributes to epithelial-mesenchymal transition in lung cancer by modulating the GSK3beta/snail/E-cadherin signaling. Oncotarget 7(9):10402–10413. https://doi.org/10.18632/oncotarget.7224

    Article  PubMed  PubMed Central  Google Scholar 

  14. Zhao S, Yi M, Yuan Y, Zhuang W, Zhang D, Yu X, Chen X, Teng B, Guan Z, Zhang Y (2015) Expression of AKAP95, Cx43, CyclinE1 and CyclinD1 in esophageal cancer and their association with the clinical and pathological parameters. Int J Clin Exp Med 8(5):7324–7332

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Foskolou IP, Stellas D, Rozani I, Lavigne MD, Politis PK (2013) Prox1 suppresses the proliferation of neuroblastoma cells via a dual action in p27-Kip1 and Cdc25A. Oncogene 32(8):947–960. https://doi.org/10.1038/onc.2012.129

    Article  CAS  PubMed  Google Scholar 

  16. Wang S, Cheng Y, Zheng Y, He Z, Chen W, Zhou W, Duan C, Zhang C (2016) PRKAR1A is a functional tumor suppressor inhibiting ERK/Snail/E-cadherin pathway in lung adenocarcinoma. Sci Rep 6:39630. https://doi.org/10.1038/srep39630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Tang S, Hou Y, Zhang H, Tu G, Yang L, Sun Y, Lang L, Tang X, Du YE, Zhou M, Yu T, Xu L, Wen S, Liu C, Liu M (2015) Oxidized ATM promotes abnormal proliferation of breast CAFs through maintaining intracellular redox homeostasis and activating the PI3K-AKT, MEK-ERK, and Wnt-beta-catenin signaling pathways. Cell Cycle 14(12):1908–1924. https://doi.org/10.1080/15384101.2015.1041685

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Bai T, Liu F, Zou F, Zhao G, Jiang Y, Liu L, Shi J, Hao D, Zhang Q, Zheng T, Zhang Y, Liu M, Li S, Qi L, Liu JY (2017) Epidermal growth factor induces proliferation of hair follicle-derived mesenchymal stem cells through epidermal growth factor receptor-mediated activation of ERK and AKT signaling pathways associated with upregulation of cyclin D1 and downregulation of p16. Stem Cells Dev 26(2):113–122. https://doi.org/10.1089/scd.2016.0234

    Article  CAS  PubMed  Google Scholar 

  19. Guo H, Luo H, Yuan H, Xia Y, Shu P, Huang X, Lu Y, Liu X, Keller ET, Sun D, Deng J, Zhang J (2017) Litchi seed extracts diminish prostate cancer progression via induction of apoptosis and attenuation of EMT through Akt/GSK-3beta signaling. Sci Rep 7:41656. https://doi.org/10.1038/srep41656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zhang X, Yu X, Jiang G, Miao Y, Wang L, Zhang Y, Liu Y, Fan C, Lin X, Dong Q, Han Q, Zhao H, Han Y, Han X, Rong X, Ding S, Wang E, Wang E (2015) Cytosolic TMEM88 promotes invasion and metastasis in lung cancer cells by binding DVLS. Cancer Res 75(21):4527–4537. https://doi.org/10.1158/0008-5472.CAN-14-3828

    Article  CAS  PubMed  Google Scholar 

  21. Hsu MK, Qiao L, Ho V, Zhang BH, Zhang H, Teoh N, Dent P, Farrell GC (2006) Ethanol reduces p38 kinase activation and cyclin D1 protein expression after partial hepatectomy in rats. J Hepatol 44(2):375–382. https://doi.org/10.1016/j.jhep.2005.07.031

    Article  CAS  PubMed  Google Scholar 

  22. Xu L, Tong X, Zhang S, Yin F, Li X, Wei H, Li C, Guo Y, Zhao J (2016) ASPP2 suppresses stem cell-like characteristics and chemoresistance by inhibiting the Src/FAK/Snail axis in hepatocellular carcinoma. Tumour Biol 37(10):13669–13677. https://doi.org/10.1007/s13277-016-5246-0

    Article  CAS  PubMed  Google Scholar 

  23. Flinder LI, Wierod L, Rosseland CM, Huitfeldt HS, Skarpen E (2013) FAK regulates Cdk2 in EGF-stimulated primary cultures of hepatocytes. J Cell Physiol 228(6):1304–1313. https://doi.org/10.1002/jcp.24287

    Article  CAS  PubMed  Google Scholar 

  24. Wang J, Huo K, Ma L, Tang L, Li D, Huang X, Yuan Y, Li C, Wang W, Guan W, Chen H, Jin C, Wei J, Zhang W, Yang Y, Liu Q, Zhou Y, Zhang C, Wu Z, Xu W, Zhang Y, Liu T, Yu D, Zhang Y, Chen L, Zhu D, Zhong X, Kang L, Gan X, Yu X, Ma Q, Yan J, Zhou L, Liu Z, Zhu Y, Zhou T, He F, Yang X (2017) Toward an understanding of the protein interaction network of the human liver. Mol Syst Biol 13(12):965. https://doi.org/10.15252/msb.20178107

    Article  PubMed  PubMed Central  Google Scholar 

  25. Menard S, Tagliabue E, Colnaghi MI (1998) The 67 kDa laminin receptor as a prognostic factor in human cancer. Breast Cancer Res Treat 52(1–3):137–145

    Article  CAS  PubMed  Google Scholar 

  26. Montuori N, Selleri C, Risitano AM, Raiola AM, Ragno P, Del Vecchio L, Rotoli B, Rossi G (1999) Expression of the 67-kDa laminin receptor in acute myeloid leukemia cells mediates adhesion to laminin and is frequently associated with monocytic differentiation. Clin Cancer Res 5(6):1465–1472

    CAS  PubMed  Google Scholar 

  27. Montuori N, Muller F, De Riu S, Fenzi G, Sobel ME, Rossi G, Vitale M (1999) Laminin receptors in differentiated thyroid tumors: restricted expression of the 67-kilodalton laminin receptor in follicular carcinoma cells. J Clin Endocrinol Metab 84(6):2086–2092. https://doi.org/10.1210/jcem.84.6.5721

    Article  CAS  PubMed  Google Scholar 

  28. Duan SG, Cheng L, Li DJ, Zhu J, Xiong Y, Li XW, Wang SG (2010) The role of MAPK-ERK pathway in 67-kDa laminin receptor-induced FasL expression in human cholangiocarcinoma cells. Dig Dis Sci 55(10):2844–2852. https://doi.org/10.1007/s10620-009-1121-9

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by the China National Science Foundation (Grant No. 81672835 to M.D.) and Scientific Research of Special-Term Professor from the Educational Department of Liaoning Province, China (Liao Cai Zhi Jiao No. 2012-512).

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Authors and Affiliations

  1. Department of General Surgery, Gastrointestinal Surgery, The First Hospital, China Medical University, No. 155 Nanjing Bei, Heping District, Shenyang, 110001, China

    Xin Li, Ming Dong, Jianping Zhou, Dehua Zhu, Jinbo Zhao & Weiwei Sheng

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  1. Xin Li
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  2. Ming Dong
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  3. Jianping Zhou
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  4. Dehua Zhu
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Correspondence to Ming Dong.

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Li, X., Dong, M., Zhou, J. et al. C6orf106 accelerates pancreatic cancer cell invasion and proliferation via activating ERK signaling pathway. Mol Cell Biochem 454, 87–95 (2019). https://doi.org/10.1007/s11010-018-3455-0

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