C6orf106 accelerates pancreatic cancer cell invasion and proliferation via activating ERK signaling pathway
- 193 Downloads
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.
KeywordsC6orf106 Pancreatic cancer ERK Invasion Proliferation
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).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 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 CrossRefPubMedGoogle 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
- 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 CrossRefPubMedPubMedCentralGoogle 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 CrossRefPubMedPubMedCentralGoogle 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 CrossRefPubMedPubMedCentralGoogle 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 CrossRefPubMedGoogle 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 CrossRefPubMedPubMedCentralGoogle 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 CrossRefPubMedGoogle 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 CrossRefPubMedGoogle 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 CrossRefPubMedPubMedCentralGoogle 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):1465–1472PubMedGoogle 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 CrossRefPubMedGoogle Scholar