ABSTRACT
ACK1 (activated Cdc42-associated kinase) is a non-receptor tyrosine kinase, originally identified by its binding to the GTP-binding small GTPase Cdc42. It is widely expressed in human tissues and activated by various extracellular growth factors such as EGF, PDGF and TGF-β. The activated ACK1 mediates the signaling cascade by interacting with downstream effectors followed by their phosphorylation. In recent years, researchers have investigated the biological functions of ACK1 and its roles in cancer research. The gene amplification and overexpression of ACK1 is associated with a poor prognosis and metastasis in a variety of cancers including lung, ovarian and prostate cancers. Therefore, the development of small molecule inhibitors of ACK1 provides promising opportunities for cancer-targeted therapy. In this review, we briefly describe recent advances in understanding the activation and biological function of ACK1 and introduce its novel inhibitors with potential therapeutic activities in preclinical studies.
ABSTRACT
Malignant colon cells require angiogenesis and optimal tumor microenvironment for proliferation, invasion and metastasis. The non-receptor tyrosine kinase signal transducer and activator of transcription (JAK-STAT) pathway are involved in multiple processes, including chronic inflammation-associated tumorigenesis, cancer proliferation, tumor angiogenesis, immune evasion and facilitating tumor metastasis, making JAK-STAT a new target in molecular target therapy. In this review, advances on JAK-STAT pathway as a new target in colon tumorigenesis are updated, and a preliminary estimation of JAK-STAT in prognosis and target therapy will be mentioned to show a potential future of JAK-STAT in colon cancer.
ABSTRACT
Objective To explore the role of non-receptor tyrosine kinase(c-Src)in sevoflurane pretreatment for relieving myocardial ischemia-reperfusion injury.Methods By using the random number table,the healthy male Wistar rats were randomly divided into 5 groups (n=10):sham operation group (Ⅰ),ischemia-reperfusion group(Ⅱ),sevoflurane pretreatment group(Ⅲ), sevoflurane pretreatment plus dimethyl sulfoxide(DMSO,Ⅳ)and sevoflurane pretreatment plus c-Src specific inhibitor SU6656 group(Ⅴ)groups.The group Ⅲ,Ⅳ and Ⅴ were performed the sevoflurane aftertreatment before reperfusion;the group Ⅴ was in-jected by SU6656 at 5 min before reperfusion;the group Ⅳ was given the equal volume DMSO.The arterial blood sample in each group was collected at 120 min after reperfusion for detecting serum LDH level and CK-MB activity.Rats were killed for taking the heart and separating the left ventricle to calculate the area of myocardial infarctio;the expression levels of Src,phosphorylated Src (p-Src),CAT and SOD in myocardial tissue were detected in each group.Results Compared with the groupⅠ,the level of serum CK-MB and LDH activity,myocardial infarct area and p-Src/Src,CAT,SOD in the other 4 groups were increased significantly (P <0.05);comparing with the group Ⅲ,the serum CK-MB and LDH activity,myocardial infarct area and SOD,CAT,in the group Ⅱ,Ⅳ and Ⅴ were increased,however the level of p-Src/Src was decreased significantly (P <0.05).Conclusion The c-Src-reactive ox-ygen signaling pathway might mediate the role of sevoflurane pretreatment for reducing myocardial ischemia-reperfusion injury in rat.