JCTJournal of Cancer Therapy2151-1934Scientific Research Publishing10.4236/jct.2013.42073JCT-29838ArticlesMedicine&Healthcare <i>STYK1/NOK</i>—A Potential Radiotherapeutic Target and Biomarker for Gastric Cancer and Cervical Cancer ingGao1XiaohuaChen2ZenghaiMa3FengshengLi4*College of Life Science and Technology, Xinjiang University, Urumchi, ChinaThe Second Artillery Journal Hospital People’s Liberation Army, Beijing, ChinaDepartment of Experimental Therapy of Acute Radiation Sickness, Beijing Institute of Radiation Medicine, Beijing, ChinaKey Laboratory of Radiological Protection and Nuclear Emergency, National Institute for Radiological Protection, China Centers for Disease Control, Beijing, China* E-mail:lifs0624@163.com(FL);110420130402575577November 30th, 2012December 31st, 2012 January 8th, 2013© Copyright 2014 by authors and Scientific Research Publishing Inc. 2014This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/

This article introduced the STYK1/NOK, including its origin, chemical composition and biological function, and the expression of STYK1/NOK in various cancer cell lines was reviewed. Furthermore, our recent study showed that STYK1/NOK protein was also over expressed in gastric cancer and cervical cancer specimens, and STYK1/NOK expression increased after tumor cells were irradiated with γ ray. These results indicated that STYK1/NOK might be involved in the occurrence and progress of gastric cancer and cervical cancer, and contribute to the radioresistance of tumor cells. Thus, STYK1/NOK might be a potential therapeutic target and diagnostic marker for gastric cancer and cervical cancer.

Gastric Cancer; Cervical Cancer; <i>STYK1/NOK</i>; Therapeutic Target1. Introduction

It is well known that receptor tyrosine kinases (RTKs) is perhaps the most important and extensively studied pathway. Ligand binding results in receptor autophosphorylation and the subsequent activation of downstream signalling cascades that include mitogen-activated protein kinase (MAPK), extracellular-signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K), phospholipase Cγ, protein kinase C and small GTPases such as Ras, Rho and RAC1 (Ras-related C3 botulinum toxin substrate 1). Abnormal expression of RTKs was believed to contribute to the tumorigenesis and progression.

STYK1 (Serine/Threonine/Tyrosine Kinase 1), also named NOK (The novel oncogene with kinase-domain) encoding a potential kinase, has been cloned in 2004 by Liu, L. et al. [1]. STYK1/NOK is approximately 30% similar to the mouse fibroblast growth factor (FGF) and plateletderived growth factor (PDGF) receptor super-family, and is predicted to have a transmembrane domain and protein kinase domain, belonging to a receptor protein tyrosine kinase family. Many studies suggested that STYK1/NOK were involved in oncogenesis and metastasis [1,2], previous studies have shown that STYK1/NOK mRNA was up-regulated in various cancer, including breast cancer and lung cancer [3,4].

2. STYK1/NOK Genes Studies Development in Gastric Cancer and Cervical Cancer

Gastric cancer was the fourth most common cancer and the second leading cause of cancer death worldwide [5-8]. It has been well proved that RTKs are involved in the occurrence and progress of gastric cancer. Furthermore, RTKs-targeted agents, such as Cetuximab [9], Trastuzumab [10-12], have been applied for treatment of the gastric cancer.

Besides melanoma cells (B16), lung cancer cells (A549), breast cancer cells (MCF-7, MDA-MD-123), the expression of STYK1/NOK was detected in gastric cancer cells (BGC823) and cervial cancer cells (Hela), Moreover, our recently study showed that STYK1/NOK protein was also over expressed in gastric cancer and cervical cancer specimens. However, the normal tissues rounding cancer expressed relative lower STYK1/NOK protein. Interestingly, real-time PCR results showed that the expression of STYK1/NOK mRNA in tumor cells increased after 2 - 10 Gy of γ-ray radiation, which indicated that STYK1/ NOK might participate in the regulation of cancer radioresistance. These results indicated that STYK1/NOK might be a potential therapeutic target and diagnostic marker for gastric cancer and cervical cancer, and treatment targeting STYK1/NOK might show a synergism with radiotherapy for gastric cancer and cervical cancer. However, there is still a long way to go for the application of STYK1/ NOK, because all the studies on STYK1/ NOK was restricted to laboratory.

3. Discussion

The human STYK1/NOK is widely expressed in human tissues with the highest abundance in the prostate, brain and heart [13]. Besides normal tissues, a variety of tumor cells also expressed the STYK1/NOK mRNAs [3], such as CRPC（castration-resistant prostate cancer）cells [14]. STYK1/ NOK could promote cell transformation, tumorigenesis, and metastasis [1]. In cells, STYK1/NOK was localised in endosomes and colocalised with epidermal growth factor receptor (EGFR) [15]. STYK1/NOK could mediate STAT3 signaling pathway, RAS/MAPK signaling pathway and PI3K/AKT signaling pathway [1,16,17], and form complexes with both Akt and GSK-3β [2]. Mutation of a tyrosine residue at Y417 site in the catalytic STYK1/NOK domain decreased the tumorigenic potential of tumor cells in vivo, suggesting an oncogenic role for STYK1/NOK [18]. Mutations both Y356F and Y356F significantly impaired Akt phosphorylation and accelerated cell death by activating caspase-3-mediated pathways, but did not affect the kinase activity of STYK1/NOK [19]. STYK1/ NOK is up-regulated in estrogen receptor-alpha negative estrogen receptor-beta positive breast cancer cells following estrogen treatment [3]. STYK1/NOK is over expressed in ovarian cancer [20], lung cancer [4], breast cancer [19] and acute leukemia [21]. STYK1/NOK mRNA expression did not correlate with c-erbB2 expression, indicating the independence of STYK1/NOK as a diagnostic marker in breast cancer of tiny tumors in which the malignancy cannot be confirmed by other means [19].

The role study of STYK1/NOK in gastric cancer and cervical cancer is not reported up to now. Our group is trying to study on this field, and obtained some results. Our preliminary results, together with previous studies, indicate that STYK1/NOK could be a possible therapeutic target and biomarker for gastric cancer and cervical cancer.

4. Acknowledgements

This work was supported by The National Natural Science Foundation of China (fund NO are 81001216 and 81202151), and the Young Scholar Scientific Research Foundation of China CDC (fund NO is 2011A202).

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