Hippo-YAP pathway is involved in the effect of NaAsO / 中国药理学通报

Aim To explore the effects of NaAsO

Hippo signaling pathway and colorectal cancer / 国际肿瘤学杂志

Hippo signaling pathway plays a significant role in the development of colorectal cancer,and acts as an important regulatory pathway which regulates cell proliferation and cell differentiation.Multiple proteins and genes in Hippo signaling pathway,especially the downstream YAP protein,play important roles in the occurrence,metastasis,drug resistance and recurrence of colorectal cancer.YAP and other related genes can be used as targeted markers for predicting drug resistance to colorectal cancer.Hippo signaling pathway gene network can be used as targeted therapy or combination therapy,thus providing new ideas for the treatment of colorectal cancer.

Regulation effect of F-actin on senescence of mesenchymal stem cells and its mechanism / 吉林大学学报(医学版)

Objective: To investigate the regulation effects of fibrous-actin (F-actin) on senescent of the human bone marrow mesenchymal stem cells (hBMSCs), and to elucidate the molecular mechanisms of senescence the of hBMSCs. Methods: The hBMSCs were cultured in vitro and divided into control group (P2 hBMSCs), F-actin inhibitor group (P2 hBMSCs were treated with 2. 5 μmol · L-1 F-actin inhibitor Latrunculin B for 1 h) and Pll hBMSCs group (Pll hBMSCs passaged from P2 hBMSCs continuously). The hBMSCs in various groups were induced by osteogenic, adipogenic and chondrogenic induction mediums and the induction effects were identified by Alizarin red staining, SO staining and oil red O staining. The number of Ki67 positive cells, polymerization and morphology of F-actin and YAP subcellular localization were detected by immunofluorescence staining. SA-β-Gal staining was uesd to detect the SA-β-Gal staining positive cells in the hBMSCs in various groups. Results: The Alizarin red staining, SO staining and oil red O staining results showed that the hBMSCs in various groups had the osteogenic, adipogenic and chondrogenic abilities. The immunofluorescence staining and SA-β-Gal staining results showed that the microfilament bundles in the hBMSCs in control group were more thick, the F-actin length was longer, and the YAP mainly concentrated in the nucleus (YAP was activated in the nucleus). Compared with control group, the number of Ki67 positive cells in Pll hBMSCs group was less and the number of SA-β-Gal positive cells was more; the Factin was shorter and thinner, the YAP mainly concentrated in the cytoplasm, and the high cytoplasmic YAP cells was positive for SA-β-Gal staining; in F-actin inhibitor group, the high cytoplasmic YAP inactivation was found in the hBMSCs and the SA-β-Gal staining positive hBMSCs had more senescent cells. Conclusion: To inhibit the entering of YAP into the nucleus can promote the senescence of hBMSCs and F-actin can affect the senescence of hBMSCs by regulating the YAP activity.

Research progress of relation between Hippo-YAP signaling pathway and tumor / 肿瘤研究与临床

The Hippo-YAP signaling pathway,an important signaling pathway of tumor suppressor,is featured by functions of adjusting the organ size and maintaining the dynamic balance between cell proliferation and apoptosis.Several researches have revealed that the Hippo-YAP signaling pathway can affect cell proliferation and apoptosis so as to participate in the development of tumor.This paper will review the effect and mechanism of Hippo-YAP signaling pathway in tumor.

Effects of Hippo pathway component on tumor recurrence after liver transplantation / 中华消化外科杂志

Objective To investigate the expression of Hippo pathway component in hepatic cancer tissues and investigate its effects on the tumor recurrence after Iiver transplantation.Methods The clinical data of 105 patients with liver cancer who were admitted to the Third Affiliated Hospital of Sun Yat-Sen University from July 2004 to September 2009 were retrospectively analyzed.The samples of liver cancer tissues were collected.The maximum diameter,number of foci,blood vessel involvement,preoperative level of alpha-fetoprotein (AFP),results of postoperative pathological examination were analyzed.All the patients were followed up via out-patient examination,mail and phone call.Patients were followed up once a week within the first month after operation,and once a month within the 6 months after operation,and then once every 3 months at 1 year later.The follow-up ended in December 2012 or tumor recurrence.The disease-free survival time began at the date of operation and ended at the time of tumor recurrence.The expressions of Yes-associated protein (YAP),phosphorylated YAP,Hippo pathway component (Lats1/2,pLats1/2,Mst1,pMst1/2) were detected by immunohistochemical staining.All data were analyzed using the chi-square test or Student t test.Factors might influence the postoperative tumorfree survival time after liver transplantation were analyzed using the Cox regression model.The survival curve was drawn by Kaplan-Meier method,and the disease-free survival was analyzed using Log-rank test.Results Positive expressions of YAP and phosphorylated YAP were detected in the nucleus and cytoplasm,and the positive expressions of Lats1/2,pLats1/2,Mst1 and pMst1/2 were detected in the cytoplasm.The positive expressions of YAP,phosphorylated YAP,Latsl/2,pLats1/2,Mst1 and pMst1/2 protein were 51.43％ (54/105),55.24％ (58/105),45.71％ (48/105),9.52％ (10/105),64.76％ (68/105) and 20.00％ (21/105),respectively.The positive expression of YAP was correlated with the tumor diameter,venous infiltration and AJCC stage (x2=4.173,9.611,7.233,P ＜ 0.05).The positive expression of Lats1/2 protein was correlated with tumor diameter and AJCC stages (x2=14.413,7.969,P ＜ 0.05).The positive expression of Mst1 protein was correlated with the tumor diameter (x2=4,129,P ＜0.05).The results of univariate analysis showed that the protein expressions of YAP,Lats1/2,pMst1/2,age,tumor diameter,tissue differentiation,preoperative level of AFP,venous infiltration and AJCC stages were risk factors influencing tumor recurrence after liver transplantation (HR =2.603,0.502,1.802,0.955,3.559,2.395,2.414,2.915,2.086,95％ CI:1.452-4.666,0.287-0.880,1.040-3.123,0.931-0.981,1.921-6.595,1.475-3.889,1.313-4.337,1.604-5.229,1.370-3.176,P ＜ 0.05).The results of multivariate analysis showed that the positive expression of YAP,tumor diameter ＞ 5 cm,low differentiation of tissue and AJCC stages Ⅲ were independent risk factors influencing tumor recurrence after liver transplantation (HR=2.011,2.176,2.390,1.574,95％CI:1.115-3.628,1.125-4.206,1.448-3.945,1.041-2.381,P ＜ 0.05).The median time of follow-up was 13.0 months (range,1.0-96.0 months).Eight patients missed follow-up.Fifty-four patients had tumor recurrence,and the mean time of tumor recurrence was 6.7 months (range,1.0-41.0 months).The disease-free survival time of patients with positive expression of YAP were significantly shorter than those with negative expression of YAP (Log-rank value =12.890,P ＜ 0.05).Conclusions Positive expressions of YAP and phosphorylated YAP were detected in the nucleus and cytoplasm,and the positive expressions of Lats1/2,pLats1/2,Mst1 and pMst1/2 were detected in the cytoplasm.The positive expression of YAP is the independent risk factor for tumor recurrence after liver transplantation.