ObjectiveTo summarize the research progress of Hippo signaling pathway in triple negative breast cancer (TNBC). MethodLiteratures about studies the role of Hippo signaling pathway in cancer stem cells, epithelial-mesenchymal transformation, tumorigenesis and development, distant metastasis, treatment resistance, and treatment strategies were retrieved. ResultsIn TNBC, overexpression of Yes-associated protein and PDZ-binding motif could promote the development of tumor stem cells, induce epithelial-mesenchymal transformation of TNBC cells, and promote tumor development, distant metastasis, and chemotherapy resistance. ConclusionHippo/Yes-associated protein axis plays an important role in carcinogenesis and progression of TNBC, and targeting Hippo signaling pathway might be a potential therapeutic target for TNBC.
The classical Hippo pathway leads to the phosphorylation of downstream effector molecules Hippo-Yes-associated protein (Yap) and transcriptional coactivator PDZ-binding motif (Taz) serine sites through a kinase response, thereby promoting cell proliferation, controlling cell polarity, changing cytoskeleton, it plays an important regulatory role in various pathophysiological processes such as epithelial-mesenchymal transition and inhibition of cell contact. Studies have shown that Yap/Taz can affect the progression of vitreoretinal diseases, opening up new prospects for the pathogenesis and clinical treatment of diabetic retinopathy, proliferative vitreoretinopathy, and retinal ischemia-reperfusion injury. Exploring the molecular mechanism of Yap/Taz provides a possible therapeutic target for future research in the treatment of retinal fibrosis diseases such as diabetic retinopathy and proliferative vitreoretinopathy. At the same time, regulating the activity of local Yap/Taz in the retina will also become an effective therapeutic target for damage-repair in retinal ischemia-reperfusion injury. However, Yap inhibitors have potential retinal toxicity and are still in the preclinical development stage. Further research on the mechanism of action and clinical safety of Yap inhibitors will provide new methods for the treatment of retinal diseases.
Objective To investigate the expression of SAPCD2 in the lung adenocarcinoma cells, and to study the effect of SAPCD2 regulating Hippo signaling pathway on the proliferation, invasion, migration and apoptosis of the lung adenocarcinoma cells and its mechanism. Methods Quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the expression levels of SAPCD2 mRNA and protein in four types of lung cancer cells (HCC827, H1650, SK-MES-1, A549) and human normal lung epithelial cells (BESA-2B), respectively. Then, lung cancer cells with relatively high levels of SAPCD2 expression were selected for subsequent experiments. The experiment cells were divided into a normal control group (NC group), a si-SAPCD2 group, and a pathway inhibitor group (si-SAPCD2+XMU-MP-1 group). Firstly, SAPCD2 mRNA was silenced using small interfering RNA (siRNA) technology, and then qRT-PCR was used to detect the expression of SAPCD2 in transfected lung cancer cells; using clone plate assay to detect the proliferation of lung cancer cells after silencing; using flow cytometry to detect the apoptosis of lung cancer cells after silencing; observe the number of lung cancer cells at different stages through cell cycle experiments; then Transwell experiment was used to analyze the effect of silencing SAPCD2 on the migration and invasion of lung cancer cell migration. Finally, Western blot was used to detect the expression of ki-67, Bcl-2, Caspase-3, NF2, P-MST1, P-LATS1, P-YAP, YAP, and TAZ proteins.Results SAPCD2 had the highest expression level in lung adenocarcinoma A549 cells (P<0.01). Silencing SAPCD2 significantly decreased the proliferation ability of A549 cells (P<0.01), inhibited their migration (P<0.05) and invasion (P<0.01), and promoted A549 cell apoptosis (P<0.01); more than half of the cells remained in the G0/G1 phase. Compared with the NC group, A549 cells showed a significant increase in G0/G1 phase cells (P<0.01), a significant decrease in G2/M and S phase cells (P<0.01), and a significant increase in the proportion of early apoptotic cells (P<0.01). Western blot results showed that silencing SAPCD2 down-regulated the expression of ki-67, Bcl-2, YAP, and TAZ proteins compared to the NC group (P<0.01), and up-regulated the expression of Caspase-3, NF2, P-MST1, P-LATS1, and P-YAP proteins (P<0.01). Conclusions The expression of SAPCD2 in lung adenocarcinoma A549 cells is significantly higher than that in normal lung epithelial cells (BESA-2B), which promotes the proliferation, migration and invasion of A549 cells and inhibits apoptosis. The mechanism may be related to the inhibition of Hippo signaling pathway.
Pulmonary hypertension is a kind of progressive pulmonary vascular diseases in which there is excessive vasoconstriction and abnormal pulmonary vascular remodeling, and then a gradual increase in pulmonary arterial pressure, and it eventually leads to right ventricular failure and even death. The pathogenesis of pulmonary hypertension is still uncertain, but some studies suggest that Hippo pathway or some components of the Hippo pathway may be involved in the progress of pulmonary hypertension. In this review, we describe the mechanism of the Hippo pathway or some components of the Hippo pathway in the progress of pulmonary hypertension.
Objective To explore the expression of yes-associated protein 1 (YAP1), as a key protein of Hippo signal pathway, in rats with brain injury. Methods A total of 18 Sprague Dawley rats were randomly divided into three groups: normal group, sham operation group and brain injury group. The expression of YAP1 in rats with brain injury was detected by immunochemistry, quantitative polymerase chainreaction and Western blotting. Result Seventy-two hours after the brain injury, the expression level of YAP1 in protein and gene increased significantly in brain injury group, compared with those in the normal and sham operation group (P<0.05). Conclusion The expression of YAP1 increases in rats with brain injury, which maybe a new target for therapy.
ObjectiveTo investigate regulation mechanism of glypican-3 (GPC3) on Hippo signaling pathway and its effects on biological behavior of hepatocellular carcinoma Huh7 cells. MethodsShort hairpin RNAs (shRNA) targeting GPC3 and Yes-associated protein 1 (YAP1) genes were constructed. All of the shRNAs were transfected into Huh7 cells by liposome transfection in order to screen out the stable expression cell lines. The expressions of GPC3 and YAP1 in Huh7 cells were detected by PCR and Western blot in order to screen out the effective shRNAs. The proliferation, invasion, and apoptosis of Huh7 cells were detected by Edu cell proliferation assay, transwell, and flow cytometry. GPC3 shRNA transfection experiments were divided into 6 groups:non-transfection group, empty vector group, GPC3-714-shRNA group, GPC3-647-shRNA group, GPC3-1718-shRNA group, and GPC3-2134-shRNA group. YAP1 shRNA transfection experiments were divided into 6 groups:non-transfection group, empty vector group, YAP1-906-shRNA group, YAP1-1363-shRNA group, YAP1-1666-shRNA group, and YAP1-2895-shRNA group. GPC3 regulation experiments were divided into 5 groups:non-transfection group, empty vector group, GPC3-1718-shRNA group, GPC3-1718-shRNA+ rhYAP1 group, and YAP1-1666-shRNA group. Results① GPC3-1718-shRNA and YAP1-1666-shRNA plasmids were successfully constructed to silence the expressions of GPC3 and YAP1. ② The expressions of GPC3 mRNA and protein in each transfection group were significantly lower than those in the non-transfection group (P<0.05) and the empty vector group (P<0.05), while which in the GPC3-1718-shRNA group was significantly lower than those in all the other transfection groups (P<0.05). The expressions of YAP1 mRNA and protein in each transfection group were significantly lower than those in the non-transfection group and empty vector group (P<0.05), while which in the YAP1-1666-shRNA group was significantly lower than those in all the other transfection groups (P<0.05). ③ The expressions of YAP1 mRNA and protein in the GPC3-1718-shRNA group and the YAP1-1666-shRNA group were significantly lower than those in the non-transfection group (P<0.05) and the empty vector group (P<0.05), while which in the GPC3-1718-shRNA+rhYAP1 group were significantly higher than those in the GPC3-1718-shRNA group (P<0.05) and the YAP1-1666-shRNA group (P<0.05). ④ Compared with the non-transfection group and the empty vector group, the abilities of cell proliferation and invasion in the GPC3-1718-shRNA group and the YAP1-1666-shRNA group were significantly decreased, and the cell apoptosis was significantly increased (P<0.05); The cell proliferation, invasion, and apoptosis in the GPC3-1718-shRNA+rhYAP1 group were significantly improved (P<0.05). ConclusionGPC3 is likely to affect biological behavior of hepatocellular carcinoma Huh7 cells through regulation of YAP1 in Hippo signaling pathway.
Objective To investigate the therapeutic effects of retinal angiomatosis in different clinical stages. To discuss the indication of vitrectomy for retinal hemangioblastoma. Methods The clinical data of 22 cases (33 eyes) were retrospectively analyzed. The retinal hemangiomas were divided into 5 stages according to their degrees of development from simple angioma without vessel dilation to feeder vessel dilation and intra-retinal exudates, local retinal detachment, massive retinal detachment and co mplication occurrence in proper order. The methods of treatment were laser photo coagulation, trans－scleral cryotherapy and vitrectomy. 13 eyes were treated with laser photocoagulation, 5 eyes with cryotherapy combined with laser and 11 eye s with vitrectomy. Tumor resection and silicone oil tamponade was performed in 3 eyes during vitrectomy. The patients were followed up for 46 months on average. Visual acuity (VA), the condition of the hemangioma and retina was compared pre- and post-operation respectively. Results In all 13 eyes treated with laser photocoagulation the hemangiomas regressed and the retina remained attached. VA improved in 2 eyes, and remained unchanged in 11 eyes. Cryother apy combined with laser photocoagulation was performed on 5 eyes. In this group, 4 eyesprime; hemangiomas regressed and no new hemangiomas occurred, proliferative vitreous retinopathy and vitreous hemorrhage was observed in 1 eye which vitrecto my was performed later. VA improved in 2 eyes, unchanged in 2 eyes and decreased in 1 eye. In the 11 eyes treated with vitreoretinal surgery, new hemangiomas wa s found in 1 eye, exudative retinal detachment was caused by hemangiomas in 2 eyes, proliferative vitreous retinopathy was observed in 2 eyes, and the retina re mained attached in 8 eyes. VA improved in 3 eyes, unimproved in 3 eyes, and decreased in 5 eyes. In the 3 eyes with surgical resection of retinal hemangioma during vitrectomy, 2 eyesprime; retina remained attached, 1 eye had exu dative retinal detachment and no new hemangiomas occurred. VA improved in 2 eyes and decreased in 1 eye. Conclusions Laser photocoagulation or combined with cryotherapy is effective in treating the hemangiomas in early stage. Vitrectomy is advisable for late stage of retinal angiomatosis, especially with vitreous hemorrhage, epiretinal membrane, proliferation and large scale of r etinal detachment. Surgical resection of isolated large retinal hemangioblastoma may be useful for selected patients. (Chin J Ocul Fundus Dis,2008,24:107-110)
【Abstract】 Objective To investigate the relationships between residual displacement of weight-bearing and non weight-bearing zones (gap displacement and step displacement) and hip function by analyzing the CT images after reconstruction of acetabular fractures. Methods The CT measures and clinical outcome were retrospectively analyzed from 48 patients with displaced acetabular fracture between June 2004 and June 2009. All patients were treated by open reduction and internal fixation, and were followed up 24 to 72 months (mean, 36 months); all fractures healed after operation. The residual displacement involved the weight-bearing zone in 30 cases (weight-bearing group), and involved the non weight-bearing zone in 18 cases (non weight-bearing group). The clinical outcomes were evaluated by Merle d’Aubigné-Postel criteria, and the reduction of articular surface by CT images, including the maximums of two indexes (gap displacement and step displacement). All the data were analyzed in accordance with the Spearman rank correlation coefficient analysis. Results There was b negative correlation between the hip function and the residual displacement values in weight-bearing group (rs= — 0.722, P=0.001). But there was no correlation between the hip function and the residual displacement values in non weight-bearing group (rs=0.481, P=0.059). The results of clinical follow-up were similar to the correlation analysis results. In weight-bearing group, the hip function had b negative correlation with step displacement (rs= — 0.825, P=0.002), but it had no correlation with gap displacement (rs=0.577, P=0.134). Conclusion In patients with acetabular fracture, the hip function has correlation not only with the extent of the residual displacement but also with the location of the residual displacement, so the residual displacement of weight-bearing zone is a key factor to affect the hip function. In patients with residual displacement in weight-bearing zone, the bigger the step displacement is, the worse the hip function is.