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Zhaowen Wang, Lei Qu, Biao Deng, Xing Sun, Shaohan Wu, Jianhua Liao, Junwei Fan, Zhihai Peng
Serine/threonine/tyrosine kinase 1 (STYK1) is known to be involved in tumor progression. However, its molecular role and mechanism in hepatocellular carcinoma (HCC) remains unknown. We evaluated the effect of STYK1 expression in HCC tissues and investigated the underlying mechanisms associated with progression. HCC tissues expressed greater levels of STYK1 than paired non-tumor tissues. Patients with HCC expressing low levels of STYK1 showed both, greater disease-free (p < 0.0001) and overall (p = 0...
2016: Scientific Reports
Mei-Yuan Chen, Hao Zhang, Jian-Xin Jiang, Cheng-Yi Sun, Chao Yu, She Tian
Intrahepatic cholangiocarcinoma (ICC) has been reported to be the second most common primary hepatic carcinoma worldwide, and very limited therapies are currently available. Serine threonine tyrosine kinase (STYK1), a member of the receptor tyrosine kinase family, exhibits tumorigenicity in many types of cancers and is a potential therapeutic target for ICC. In this study, STYK1 was knocked down in the ICC cell lines HCCC-9810 and RBE via a lentivirus-mediated system using short hairpin RNA (shRNA). Next, cell proliferation, colony formation, cell cycle progression, tumor formation in nude mice, migration and invasion, and the expression levels of cell cycle proteins in Lv-sh STYK1- or Lv-sh Con-infected cells were analyzed by CCK-8 assay, colony formation evaluation, flow cytometry, tumor formation evaluation, wound scratch assay, transwell assay, and western blotting...
August 19, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Yue Liu, Tianqi Li, Dan Hu, Shuping Zhang
Previous studies have indicated that the overexpression of NOK, also named STYK1, led to tumorigenesis and metastasis. Here, we provide evidence that increased expression of NOK/STYK1 caused marked alterations in the overall and inner structures of tumors and substantially facilitates the genesis and remodeling of the blood and lymphatic vessels during tumor progression. In particular, NOK-expressed HeLa stable cells (HeLa-K) significantly enhanced tumor growth and metastasis in xenografted nude mice. Hematoxylin and eosin (HE) staining demonstrated that the tumor tissues generated by HeLa-K cells were much more ichorous and had more interspaces than those generated by control HeLa cells (HeLa-C)...
September 9, 2016: Biochemical and Biophysical Research Communications
Sheng-Qi Hou, Li Liu
The novel oncogene with kinase-domain (NOK), is an atypical receptor protein tyrosine kinase with potent oncogenic potential. In the current study, we generated two point mutations (P203L and V395I) on NOK gene. NOK(P203L) is identical to serine/threonine/tyrosine kinase 1 (STYK1), the aliases of NOK, while the V395I mutation was recovered from human glioblastoma. Both mutations did not impair NOK kinase activities, but V395I inhibited NOK autophosphorylation. Although with overall inhibition, both STYK1 and V395I affected the activities of extracellular regulated protein kinase (ERK), Akt and signal transducer and activator of transcription (STAT) differently in HEK293T cells versus HeLa and BaF3 stable cells The proliferation potentials for both STYK1 and V395I were significantly inhibited...
2015: Frontiers in Bioscience (Landmark Edition)
Liang Hu, Hai-Yang Chen, Jian Cai, Yu Zhang, Chen-Ye Qi, Hui Gong, Yan-Xia Zhai, Hao Fu, Guang-Zhen Yang, Chun-Fang Gao
BACKGROUND: Aberrant expression of serine threonine tyrosine kinase 1 (STYK1) has been reported in several human malignancies including colorectal cancer (CRC). However, the prognostic significance of STYK1 expression in CRC remains unknown. METHODS: STYK1 protein expression in paraffin-embedded CRC specimens was determined immunohistochemically. The correlation of STYK1 expression with clinicopathologic features was assessed in a cohort containing 353 patients with primary CRC...
2015: BMC Cancer
Shinya Nirasawa, Daisuke Kobayashi, Takashi Kondoh, Kageaki Kuribayashi, Maki Tanaka, Nozomi Yanagihara, Naoki Watanabe
Alterations in the mRNA expression or the mutation of previously reported tyrosine kinases have been detected only in a limited number of patients with acute leukemia. In this study, we examined whether the widely expressed serine threonine tyrosine kinase 1 (STYK1)/novel oncogene with kinase domain (NOK) acts as a drug resistance factor in acute leukemia. The transfection of leukemic HL-60 cells with an STYK1 expression vector resulted in the resistance to doxorubicin and etoposide and decreased drug-induced caspase-3/7 activity and sub-G1 population...
November 2014: International Journal of Oncology
Ayla Valinezhad Orang, Reza Safaralizadeh, Mohammad Ali Hosseinpour Feizi, Mohammad Hossein Somi
BACKGROUND: Alterations in gene expression levels or mutations of tyrosine kinases are detected in some human cancers. In this study, we examined whether serine threonine tyrosine kinase 1 (STYK1)/novel oncogene with kinase domain (NOK) is overexpressed in patients with colorectal cancer. We also examined the clinical relevance of STYK1/NOK expression in cancer tissues. MATERIALS AND METHODS: In tumor samples of patients with colorectal cancer and their matched non-cancerous samples, STYK1/NOK messenger RNA (mRNA) expression was analyzed by quantitative reverse transcriptase polymerase chain reaction...
2014: Asian Pacific Journal of Cancer Prevention: APJCP
Peng Chen, Wei-Miao Li, Qiang Lu, Jian Wang, Xiao-Long Yan, Zhi-Pei Zhang, Xiao-Fei Li
BACKGROUND: The expression of novel oncogenic kinase (NOK), a member of the protein tyrosine kinase (PTK) family, has been observed in several human malignancies including non-small cell lung cancer (NSCLC). However, the clinic relevance of NOK expression in NSCLC remains unclear. METHODS: In this study, NOK expression in tumor cells was assessed using immunohistochemical methods in 191 patients with resected NSCLC. The association of NOK expression with clinicopathological parameters, including the Ki-67 labeling index (LI), was also evaluated...
2014: BMC Cancer
Jing Li, Fang Wu, Feng Sheng, Yi-Jia Li, Da Jin, Xue Ding, Shuping Zhang
NOK (also known as STYK1) has been identified as an oncogene. However, its biochemical and biological activities as a molecular regulator are poorly defined. In the present study, we report that NOK overexpression led to enhanced phosphorylation of GSK-3β at its Ser9 residue via Akt phosphorylation at Thr308. NOK could make complexes with both Akt and GSK-3β. Moreover, the expression levels of NOK, p-Akt(Thr308) and p-GSK-3β(Ser9) were positively correlated in cancerous and non-cancerous breast cell lines...
November 2, 2012: FEBS Letters
Xue Ding, Qing-Bo Jiang, Rui Li, Shaoyong Chen, Shuping Zhang
Our previous studies showed that the overexpression of Novel Oncogene with Kinase-domain (NOK)/STYK1 led to cellular transformation, tumorigenesis and metastasis. This report characterises the subcellular distribution of NOK in HeLa cells and its localisation in early endosomes. Confocal immunolocalisation studies indicated that NOK had structural subtypes and was distributed into two distinct expression patterns: a dot pattern (DP) and an aggregation pattern (AP). The results of an immunohistochemistry (IHC) analysis of pathological tissues also showed that high expression level of endogenous NOK was expressed in an aggregate-like structure in vivo...
May 11, 2012: Biochemical and Biophysical Research Communications
Kesmic A Jackson, Gabriela Oprea, Jeffrey Handy, K Sean Kimbro
BACKGROUND: Overexpression of STYK1, a putative serine/threonine and tyrosine receptor protein kinase has been shown to confer tumorigenicity and metastatic potential to normal cells injected into nude mice. Mutation of a tyrosine residue in the catalytic STYK1 domain attenuates the tumorigenic potential of tumor cells in vivo, collectively, suggesting an oncogenic role for STYK1. METHODS: To investigate the role of STYK1 expression in ovarian cancer, a panel of normal, benign, and ovarian cancer tissues was evaluated for STYK1 immunoreactivity using STYK1 antibodies...
2009: Journal of Ovarian Research
Suyoun Chung, Kenji Tamura, Mutsuo Furihata, Motohide Uemura, Yataro Daigo, Yasutomo Nasu, Tsuneharu Miki, Taro Shuin, Tomoaki Fujioka, Yusuke Nakamura, Hidewaki Nakagawa
Despite high response rates and clinical benefits, androgen ablation often fails to cure advanced or relapsed prostate cancer because castration-resistant prostate cancer (CRPC) cells inevitably emerge. CRPC cells not only grow under castration, but also behave more aggressively, indicating that a number of malignant signaling pathways are activated in CRPC cells as well as androgen receptor signaling. Based on information from the gene expression profiles of clinical CRPC cells, we here identified one overexpressed gene, serine/threonine/tyrosine kinase 1 (STYK1), encoding a potential kinase, as a molecular target for CRPC...
November 2009: Cancer Science
Takashi Kondoh, Daisuke Kobayashi, Naoki Tsuji, Kageaki Kuribayashi, Naoki Watanabe
OBJECTIVE: Alterations in gene expression levels or mutations of previously reported tyrosine kinases are detected in only limited numbers of patients with acute leukemia. In this study, we examined whether serine threonine tyrosine kinase 1 (STYK1)/novel oncogene with kinase domain (NOK) is overexpressed in patients with acute leukemia. MATERIALS AND METHODS: In peripheral blood cells from nonleukemic group and acute leukemic patients, STYK1/NOK messenger RNA (mRNA) expression was analyzed by quantitaive reverse transcriptase polymerase chain reaction...
July 2009: Experimental Hematology
K Sean Kimbro, Kaitlin Duschene, Margeret Willard, Jodi-Ann Moore, Shalonda Freeman
The human STYK1/NOK protein is approximately 30-35% similar to mouse fibroblast growth factor receptor 3 and a kinase homologue in D. melanogaster in the tyrosine protein kinase region. STYK1/NOK was identified as being up regulated in MDA-MB-231, an estrogen receptor-alpha negative breast cancer cell line, following 12 h of estrogen treatment at 1x10(-9) M. On further investigation of STYK1/NOK in estrogen treated cell line MDA-MB-231, STYK1/NOK was up regulated at 6 h post treatment when compared to untreated cells...
March 2008: Molecular Biology Reports
Xin Ye, Chaoneng Ji, Qingshan Huang, Chao Cheng, Rong Tang, Jian Xu, Li Zeng, Jianfeng Dai, Qihan Wu, Shaohua Gu, Yi Xie, Yumin Mao
Protein kinases (PKs) represent a well studied but most diverse protein superfamily. The covalent, reversible linkage of phosphate to serine, threonine, and tyrosine residues of substrate proteins by protein kinases is probably ubiquitous cellular mechanism for regulation of physiological processes. It is known to us that most signaling pathways impinge at some point on protein kinases. Here we report a human putative receptor protein kinase cDNA STYK1. The STYK1 cDNA is 2749 base pairs in length and contains an open reading frame encoding 422 amino acids...
June 2003: Molecular Biology Reports
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