KIF2C: a novel link between Wnt/β-catenin and mTORC1 signaling in the pathogenesis of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is the fourth-leading cause of cancer-related deaths worldwide. HCC is refractory to many standard cancer treatments and the prognosis is often poor, highlighting a pressing need to identify biomarkers of aggressiveness and potential targets for future treatments. Kinesin family member 2C (KIF2C) is reported to be highly expressed in several human tumors. Nevertheless, the molecular mechanisms underlying the role of KIF2C in tumor development and progression have not been investigated. In this study, we found that KIF2C expression was significantly upregulated in HCC, and that KIF2C up-regulation was associated with a poor prognosis. Utilizing both gain and loss of function assays, we showed that KIF2C promoted HCC cell proliferation, migration, invasion, and metastasis both in vitro and in vivo. Mechanistically, we identified TBC1D7 as a binding partner of KIF2C, and this interaction disrupts the formation of the TSC complex, resulting in the enhancement of mammalian target of rapamycin complex1 (mTORC1) signal transduction. Additionally, we found that KIF2C is a direct target of the Wnt/β-catenin pathway, and acts as a key factor in mediating the crosstalk between Wnt/β-catenin and mTORC1 signaling. Thus, the results of our study establish a link between Wnt/β-catenin and mTORC1 signaling, which highlights the potential of KIF2C as a therapeutic target for the treatment of HCC.

Effect of PARP1 through regulating NFATs on cardiac hypertrophy / 中国药理学通报

Aim To investigate the interaction and mechanism of PARP1 and NFATc3, NFATc4 in ISO-induced pathological cardiac hypertrophy. Methods To establish the model of cardiac hypertrophy in vitro and in vivo, primary neonatal rat cardiomyocytes were treated with ISO (10 jimol • L-1) for 24 h; SD rats were subcutaneously injected with 1. 2 mg • kg-1 • d-1 ISO for 7 d. The nuclear and cytoplasmic proteins were separated by Cellytic Nuclear Extraction Kit. The subcellular localization of NFATc3 and NAFTc4 were detected by Western blot and immunofluorescence. The recombinant adenovirus (Ad-PARPl) infection was used to overexpress PARP1 and knockdown PARP1 by transfecting with siRNA of PARP1 in cardiomyocytes. Results The models of cardiac hypertrophy were successfully built both in vivo and vitro by ISO. It was determined that NFATc3 and NFATc4 were transfered into the nuclear from the cytoplasm in primary neonatal rat cardiomyocytes (NRCMs) after being treated with ISO. And the enzymatic activity of PARP1 was boosted in TSO-trpatpH prmin. OvprpYnrp.ssinn of PARP1 nromo-ted the nuclear translocation of NFATc3 and NFATc4 in cardiomyocytes, while knockdown of PARP1 could reverse the nuclear translocation induced by ISO. PARP1 inhibitor 3AB retarded ISO-induced nuclear transportation of NFATc3 and NFATc4 to some extent. Conclusions ISO leads to the up-regulation of enzymatic activity of PARP1 and promotes nuclear translocation of NFATc3 and NFATc4, thus aggravating car-diac hypertrophy.

Present situation and advances on the nimotuzumab related radiosensitivity research / 实用肿瘤学杂志

With data support from abundant research ,epithelial growth factor receptor ( EGFR) signaling pathway is associated with radiotherapy resistance .EGFR inhibition has become one of methods to increase radio-sensitivity.As the first EGFR monoclonal antibody developed by China and Cuba ,nimotuzumab demonstrates its distinct clinical characteristics and has been extensively explored in head and neck cancer , esophageal cancer , high grade glioma .This article mainly reviews the present situation and recent advances on the radiosensitivity re -search of nimotuzumab .