SPHK1 promotes metastasis of thyroid carcinoma through activation of the S1P/S1PR3/Notch signaling pathway.
作者： Zhijing Zhao , Junfeng Ma , Baoquan Hu , Yi Zhang , Shushu Wang
关键词:
摘要: Thyroid carcinoma is characterized by an aggressive behavior, lack of effective targeted therapies and a high rate relapse. Sphingosine kinase 1 (SPHK1) has been reported to be critical regulatory factor in the progression thyroid carcinoma, but correlation between SPHK1 clinical prognosis patients with remained fully elucidated. The present study aimed systematically assess roles metastasis further investigate possible underlying mechanisms. First, expression was detected tissue samples from 53 cell lines reverse transcription-quantitative polymerase chain reaction analysis. Furthermore, level phospho-(p)-SPHK1 immunohistochemically human samples. activity measured commercial Activity Assay kit. A sphingosine-1-phosphate (S1P) competitive ELISA kit used determine extracellular S1P levels. metastatic potential assessed Transwell assay. In addition, association clinicopathological features analyzed. results indicated that significantly higher than paired adjacent normal tissues. High levels were positively correlated poor overall survival progression-free survival. Downregulation lentiviral vector expressing small interfering (si)RNA evidently repressed Notch signaling reduced migration invasion cells vitro NOD/SCID mouse model. inhibition siRNA or treatment inhibitor 5C sensitized cisplatin doxorubicin. it demonstrated silencing effectively inhibits processes associated through pathway, may therefore represent therapeutic target carcinoma. conclusion, p-SPHK1 which turn promoted via S1P/S1P receptor 3/Notch suggesting prognostic markers targets.
sci-hub.se 参考文章(35)
Pol Sanllehí, José-Luis Abad, Josefina Casas, Antonio Delgado, Inhibitors of sphingosine-1-phosphate metabolism (sphingosine kinases and sphingosine-1-phosphate lyase). Chemistry and Physics of Lipids. ,vol. 197, pp. 69- 81 ,(2016) , 10.1016/J.CHEMPHYSLIP.2015.07.007
Yoon Ju Bae, Michael Schaab, Juergen Kratzsch, Calcitonin as Biomarker for the Medullary Thyroid Carcinoma. Recent results in cancer research. ,vol. 204, pp. 117- 137 ,(2015) , 10.1007/978-3-319-22542-5_5
Shuntaro Tsukamoto, Yuhui Huang, Motofumi Kumazoe, Connie Lesnick, Shuhei Yamada, Naoki Ueda, Takashi Suzuki, Shuya Yamashita, Yoon Hee Kim, Yoshinori Fujimura, Daisuke Miura, Neil E. Kay, Tait D. Shanafelt, Hirofumi Tachibana, Sphingosine kinase-1 protects multiple myeloma from apoptosis driven by cancer specific inhibition of RTKs Molecular Cancer Therapeutics. ,vol. 14, pp. 2303- 2312 ,(2015) , 10.1158/1535-7163.MCT-15-0185
D. Schmid, C. Ricci, G. Behrens, M. F. Leitzmann, Adiposity and risk of thyroid cancer: a systematic review and meta-analysis Obesity Reviews. ,vol. 16, pp. 1042- 1054 ,(2015) , 10.1111/OBR.12321
Masashi Murakami, Masatoshi Ichihara, Sayaka Sobue, Ryosuke Kikuchi, Hiromi Ito, Ami Kimura, Takashi Iwasaki, Akira Takagi, Tetsuhito Kojima, Masahide Takahashi, Motoshi Suzuki, Yoshiko Banno, Yoshinori Nozawa, Takashi Murate, RET signaling-induced SPHK1 gene expression plays a role in both GDNF-induced differentiation and MEN2-type oncogenesis Journal of Neurochemistry. ,vol. 102, pp. 1585- 1594 ,(2007) , 10.1111/J.1471-4159.2007.04673.X
Franclim Ricardo Ribeiro, Ana Margarida Meireles, Ana Sofia Rocha, Manuel Rodrigues Teixeira, Conventional and molecular cytogenetics of human non-medullary thyroid carcinoma: characterization of eight cell line models and review of the literature on clinical samples BMC Cancer. ,vol. 8, pp. 371- 371 ,(2008) , 10.1186/1471-2407-8-371
Zijie Zhang, Zhenyu Yan, Zheng Yuan, Yanzhen Sun, Haifa He, Chunyang Mai, SPHK1 inhibitor suppresses cell proliferation and invasion associated with the inhibition of NF-κB pathway in hepatocellular carcinoma. Tumor Biology. ,vol. 36, pp. 1503- 1509 ,(2015) , 10.1007/S13277-014-2665-7
Long Shuang Huang, Viswanathan Natarajan, Sphingolipids in pulmonary fibrosis Advances in Biological Regulation. ,vol. 57, pp. 55- 63 ,(2015) , 10.1016/J.JBIOR.2014.09.008
Huiping Zhou, Eric Kwong, Yunzhou Li, Phillip B. Hylemon, Bile acids and sphingosine-1-phosphate receptor 2 in hepatic lipid metabolism. Acta Pharmaceutica Sinica B. ,vol. 5, pp. 151- 157 ,(2015) , 10.1016/J.APSB.2014.12.009
Taro Okada, Guo Ding, Hirofumi Sonoda, Taketoshi Kajimoto, Yuki Haga, Ali Khosrowbeygi, Sanyang Gao, Noriko Miwa, Saleem Jahangeer, Shun-ichi Nakamura, Involvement of N-terminal-extended form of sphingosine kinase 2 in serum-dependent regulation of cell proliferation and apoptosis. Journal of Biological Chemistry. ,vol. 280, pp. 36318- 36325 ,(2005) , 10.1074/JBC.M504507200