Alisol A Inhibited the Proliferation, Migration, and Invasion of Nasopharyngeal Carcinoma Cells by Inhibiting the Hippo Signaling Pathway

Abstract BackgroundLong noncoding RNAs (lncRNAs) play an important role in the regulation of gene expression and are involved in several pathological responses. However, many important lncRNAs in breast cancer have not been identified and their expression levels and functions in breast cancer remain unknown.MethodsWe used the microarray data to identify differentially expressed lncRNAs between breast cancer and adjacent breast epithelial tissues. In vitro and in vivo assays were used to explore the biological effects of the differentially expressed lncRNA Apoptosis-Associated Transcript in Bladder Cancer (AATBC) in breast cancer cells. The mass spectrometry and RNA pulldown were used to screen AATBC interacting proteins. Using the Kaplan-Meier method, survival analysis was performed.ResultsThe expression of AATBC was significantly high in breast cancer samples, and this high AATBC level was tightly correlated with poor prognosis in breast cancer patients. In vitro and in vivo experiments indicated that AATBC promoted breast cancer cells migration and invasion. AATBC specifically interacted with Y-box binding protein 1 (YBX1), which activated the YAP1/Hippo signaling pathway by binding to macrophage stimulating 1 (MST1) and promoting the nuclear translocation of Yes associated protein 1 (YAP1), allowing its function as a nuclear transcriptional regulator. ConclusionsAATBC is highly expressed in breast cancer and contributes to patients’ progression, indicating that it could serve as a novel prognostic marker for the disease. Mechanistically, AATBC affects migration and invasion of breast cancer cells through an AATBC-YBX1-MST1 axis, resulting in activating the YAP1/Hippo signaling pathway. This is also an important supplement to the composition of the YAP1/Hippo signaling pathway. The model of “AATBC-YAP1” may bring a new dawn to the treatment of breast cancer.

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LTBP4 Inhibits the Proliferation and Metastasis in Melanoma by Activating Hippo-YAP Signaling

10.21203/rs.3.rs-115116/v1 ◽

2020 ◽

Author(s):

Li na Wang ◽

Dong run Tang ◽

Tong Wu ◽

Feng yuan Sun

Keyword(s):

Cell Proliferation ◽

Signaling Pathway ◽

Western Blotting ◽

Nuclear Translocation ◽

Tumor Formation ◽

Migration And Invasion ◽

Hippo Signaling ◽

Ppi Network ◽

Hippo Signaling Pathway ◽

Proliferation And Metastasis

Abstract Background: Malignant melanoma is the deadliest of skin cancer. The present study aimed to elucidate potential key candidate genes in melanoma and its molecular mechanism. Methods: Three gene expression profile data sets (GSE46517, GSE52882 and GSE54493) were downloaded from the GEO database, which included data from melanoma tissue samples and cell lines. DEGs were subsequently investigated by GO analysis via using DAVID website. PPI network was constructed using the STRING database and visualized by Cytoscape software and MCODE were utilized to PPI network to pick out meaningful DEGs. Cell proliferation, apoptosis, migration and invasion were measured using CCK-8, colony formation, flow cytometry, transwell and wound healing assays. RT-PCR, western blotting and immunohistochemistry assays were used to detect mRNA and protein expressions. TCGAportal and GEPIA databases were used to perform the bioinformatics analysis of LTBP4 in melanoma. Results: LTBP4 both is the DEG and a key gene from the most significant module of the PPI network. LTBP4 expression was down-regulation in melanoma tissues and cells relative to controls, which showed positive correlation with invasion, TNM stage, distal metastasis and lymph node metastasis, and predicted the poor prognosis for patients with melanoma. Cox analysis identified LTBP4 low-expression as an independent prognostic variable for overall survival (OS) in patients with melanoma. The results revealed that LTBP4 inhibition reduced cell apoptosis, promoted cell proliferation and metastasis. These changes were correlated caspase-3, ki67 and E-cadherin expressions by western blotting assay. Further in vivo tumor formation study in nude mice indicated that LTBP4 inhibition promoted the progress of tumor formation. LTBP4 gene knockout reduced the phosphorylation level of YAP, MST1 and MOB1 and promoted the nuclear translocation of YAP to inhibit the activation of Hippo signaling pathway. The functions of LTBP4 overexpression (OE) inhibiting the expressions of CTGF, Cyr61 and Birc5, promoting the apoptosis, and inhibiting the metastasis and proliferation of melanoma cells were reversed by YAP/or MST1 OE.Conclusions: LTBP4 OE suppressed the proliferation and metastasis in melanoma via inhibiting the nuclear translocation of YAP to activating Hippo signaling pathway, thereby inhibiting the development and progression of melanoma.

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Jiedu Sangen Decoction Inhibits the Invasion and Metastasis of Colorectal Cancer Cells by Regulating EMT through the Hippo Signaling Pathway

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/1431726 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Li Yuan ◽

Mengmeng Zhou ◽

Harpreet S. Wasan ◽

Kai Zhang ◽

Zhaoyi Li ◽

...

Keyword(s):

Colorectal Cancer ◽

Signaling Pathway ◽

Epithelial Mesenchymal Transition ◽

Migration And Invasion ◽

Binding Motif ◽

Hippo Signaling ◽

Invasion And Metastasis ◽

Mesenchymal Transition ◽

Hippo Signaling Pathway ◽

Sw480 Cells

Colorectal cancer (CRC) is one of the most common malignant tumors affecting the digestive tract. Moreover, the invasion and metastasis of CRC are the main reason therapy is usually inefficient. Decreased intercellular adhesion and enhanced cell motility induced by epithelial-mesenchymal transition (EMT) provide the basic conditions for the invasion and metastasis of the epithelial tumor cells of CRC. The Jiedu Sangen Decoction (JSD) is a prescription that has been used for more than 50 years in the treatment of CRC in the Zhejiang Hospital of Traditional Chinese Medicine. The aim of this study was to investigate the mechanism of JSD-triggered inhibition of invasion and metastasis in colon cancer. In vitro, the EMT model of the SW480 cells was induced by using epithelial growth factor (50 ng/mL). In vivo, the murine model of liver metastasis was constructed by inoculating mice with the SW480 cells. The effects of JSD on cell migration, invasion, and proliferation were determined using the transwell assay and CCK-8 assay. Moreover, the proteins related to the EMT process and the Hippo signaling pathway in the cancerous tissues and cell lines were determined by western blotting and immunostaining. JSD could significantly inhibit the proliferation, migration, and invasion of CRC cells and reverse their EMT status (all, P < 0.05). Moreover, after intervention with JSD, the levels of E-Cadherin (E-cad) increased, whereas the expression levels of N-Cadherin (N-cad), Yes-associated protein (YAP), and the transcriptional coactivator with the PDZ-binding motif (TAZ) decreased in both the SW480 cells and the tumor tissues. In summary, JSD reversed EMT and inhibited the invasion and metastasis of CRC cells through the Hippo signaling pathway.

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The long noncoding RNA AATBC promotes breast cancer migration and invasion by interacting with YBX1 and activating the YAP1/Hippo signaling pathway

Cancer Letters ◽

10.1016/j.canlet.2021.04.025 ◽

2021 ◽

Author(s):

Maonan Wang ◽

Manli Dai ◽

Dan Wang ◽

Ting Tang ◽

Fang Xiong ◽

...

Keyword(s):

Breast Cancer ◽

Signaling Pathway ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Migration And Invasion ◽

Hippo Signaling ◽

Hippo Signaling Pathway ◽

Cancer Migration

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Nitidine chloride possesses anticancer property in lung cancer cells through activating Hippo signaling pathway

Cell Death Discovery ◽

10.1038/s41420-020-00326-7 ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Jing Zhang ◽

Linhui Wu ◽

Chaoqun Lian ◽

Shuo Lian ◽

Shimeng Bao ◽

...

Keyword(s):

Cell Cycle ◽

Western Blot ◽

Signaling Pathway ◽

Migration And Invasion ◽

Hippo Signaling ◽

Protein Expression Level ◽

Hippo Signaling Pathway ◽

Proliferation Ability ◽

And Migration ◽

Western Blot Data

Abstract Nitidine chloride (NC) has significant anti-tumor properties; however, the precise mechanism related to NC still needs further investigation. This study intends to investigate the anti-tumor functions and the feasible molecular basis of NC in NSCLC cells. Therefore, we determined the mechanism of NC-mediated anti-tumor function through various methods. Cell proliferation ability and migration and invasion were detected by CCK-8, colony formation assay and Transwell assay, respectively. Furthermore, flow cytometry was used to detect apoptosis, cell cycle and ROS. Moreover, protein expression level was measured by western blot. Our results showed that NC can inhibit the growth, motility of NSCLC cells, induce apoptosis and arrest cell cycle. Meanwhile, NC increased the level of ROS in NSCLC cells. Moreover, western blot data showed that NC suppressed the expression of Lats1, Mob1, and YAP, and enhanced the expression of p-Lats1, p-Mob1, p-YAP1 (ser127). Overall, our research reveals that NC exerts anticancer activity by activating and modulating the Hippo signaling pathway.

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Targeting tumor microenvironment: Metformin suppresses IL-22 induced hepatocellular carcinoma by upregulating Hippo signaling pathway

10.21203/rs.3.rs-35094/v1 ◽

2020 ◽

Author(s):

Dong Zhao ◽

Tao Zhou ◽

Yi Luo ◽

Chenchen Wang ◽

Dongwei Xu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Signaling Pathway ◽

Hippo Pathway ◽

Ectopic Expression ◽

Tumor Development ◽

Migration And Invasion ◽

Hippo Signaling ◽

Hippo Signaling Pathway

Abstract BackgroundEpidemiological studies have shown direct associations between type 2 diabetes and the risk of cancers. Accumulating evidence indicates that metformin is profoundly implicated in preventing tumor development. However, the exact mechanism underlying the anti-tumor effects of metformin in hepatocellular carcinoma (HCC) is still not clear. MethodsIn this study, we investigated the effects of metformin on a mouse hepatocellular carcinoma (HCC) model and interleukin-22 (IL-22)-associated carcinogenesis in vitro.ResultsWe found that metformin significantly suppressed the incidence and tumor burden of HCC in the diethyl-nitrosamine (DEN)-induced HCC mouse model. As expected, expression of IL-22, an important factor involved in HCC progression, was markedly reduced by metformin. Treatment of HCC cells with metformin inhibited IL-22 induced cell proliferation, migration and invasion, and promoted cell apoptosis. Furthermore, ectopic expression of IL-22 makes HCC more aggressive whereas metformin largely compromised it in vitro and in vivo. Mechanistically, the whole transcriptome analysis and functional analysis revealed that Hippo signaling pathway was involved in the anti-tumor ability of metformin. Consistent with this, metformin directly activated Mst1/2, phosphorylated YAP1 in vitro. After blocking Hippo pathway by XMU-MP-1, the inhibitor of MST1/2, the inhibitory effects by metformin were dramatically attenuated as shown by in vitro study.ConclusionsCollectively, our findings illuminate a new regulatory mechanism, metformin activates Hippo signaling pathway to regulate IL-22 mediated HCC progression and provide new insights into its tumor-suppressive roles.

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miR-24-3p Promotes Cell Proliferation, Migration, and Invasion of Human Cervical Cancer Cells through/via Targeting AMOTL2 and Attenuating the YAP/Hippo Pathway

10.21203/rs.3.rs-708235/v1 ◽

2021 ◽

Author(s):

Yiyun Huang ◽

Lijun Hu ◽

Lu Lin ◽

Yan Liu ◽

Yan Zhang ◽

...

Keyword(s):

Cervical Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Signaling Pathway ◽

Target Genes ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Hippo Signaling ◽

Hippo Signaling Pathway ◽

Cervical Cancer Cells

Abstract BackgroundmiR-24-3p promotes the development of the majority of malignancies.However, its function in cervical cancer is not clearly elucidated so far.MethodsIn this study, cell proliferation, migration, and invasion were measured by the CCK8 and transwell assays. Bioinformatic methods were used to predict the target genes of miR-24-3p, verifying by luciferase reporter assay and western blotting. The target genes set was also used for KEGG pathway enrichment analysis. ResultsThen we obsrved higher miR-24-3p level in cervical cancer cells and faster growth of tumor in a xenograft model. The function assays demonstrated that miR-24-3p promoted proliferation, migration, and invasion of cervical cancer cells in vitro. It was confirmed that miR-24-3p directly targeted AMOTL2 and the recovery of AMOTL2 reversed the function of miR-24-3p in cervical cancer cell line CaSki. Besides, miR-24-3p suppressed the Hippo signaling pathway in CaSki and SiHa cells. ConclusionsIn conclusion, our results reminded that miR-24-3p could boost the migration and proliferation of cervical cancer cells via down-regulating AMOTL2 and attenuating YAP/Hippo signaling pathway activity.

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miR-574-5p Targets FOXN3 to Regulate the Invasion of Nasopharyngeal Carcinoma Cells via Wnt/β-Catenin Pathway

Technology in Cancer Research & Treatment ◽

10.1177/1533033820971659 ◽

2020 ◽

Vol 19 ◽

pp. 153303382097165

Author(s):

Zhonghao Lin ◽

Miaoan Chen ◽

Yawen Wan ◽

Liguang Lei ◽

Huiqing Ruan

Keyword(s):

Cell Proliferation ◽

Nasopharyngeal Carcinoma ◽

Signaling Pathway ◽

Target Gene ◽

Carcinoma Cells ◽

Migration And Invasion ◽

Promoting Effect ◽

Protein Coding ◽

Rna Molecules ◽

Forkhead Box

MicroRNAs (miR) are a class of non-coding endogenous RNA molecules that suppress the translation of protein-coding genes by destabilizing target mRNAs. The MiR-574-5p has been reported to be involved in the several types of cancer. However, the expression of miR-574-5p and its mechanism in nasopharyngeal carcinoma (NPC) remain unclear. We found that the expression level of miR-574-5p was significantly increased in the NPC cell lines. We further demonstrated that Forkhead box N3 (FOXN3) was a target gene of miR-574-5p. FOXN3 overexpression and inhibition reversed the promoting or suppressing effect, respectively, of NPC cell proliferation, migration and invasion caused by miR-574-5p. Furthermore, miR-574-5p enhanced the β-catenin and TCF4 protein expression by repressing FOXN3 expression, resulting in the activation of the Wnt/β-catenin signaling pathway, but the activity of the Wnt/β-catenin signaling pathway was inhibited by a miR-574-5p inhibitor or FOXN3 overexpression, which reversed the effect of miR-574-5p. Wound-healing and Transwell assays also showed that miR-574-5p promotes the cell migration and invasion of NPC cells, whereas the promoting effect of miR-574-5p was also reversed by a miR-574-5p inhibitor or FOXN3 overexpression. Collectively, these data suggested that miR-574-5p promotes NPC cell proliferation, migration, and invasion at least partly by targeting the FOXN3/Wnt/β-Catenin signaling pathway.

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Targeting Tumor Microenvironment: Metformin Suppresses IL-22 Induced Hepatocellular Carcinoma by Upregulating Hippo Signalling Pathway.

10.21203/rs.3.rs-41517/v1 ◽

2020 ◽

Author(s):

Dong Zhao ◽

Tao Zhou ◽

Yi Luo ◽

Chenchen Wang ◽

Dongwei Xu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Signaling Pathway ◽

Ectopic Expression ◽

Tumor Development ◽

In Vitro Study ◽

Migration And Invasion ◽

Hippo Signaling ◽

Hippo Signaling Pathway

Abstract Background: Epidemiological studies have shown direct associations between type 2 diabetes and the risk of cancers. Accumulating evidence indicates that metformin is profoundly implicated in preventing tumor development. However, the exact mechanism underlying the anti-tumor effects of metformin in hepatocellular carcinoma (HCC) is still not clear. Methods: In this study, we investigated the effects of metformin on a mouse hepatocellular carcinoma (HCC) model and interleukin-22 (IL-22)-associated carcinogenesis in vitro. Results: We found that metformin significantly suppressed the incidence and tumor burden of HCC in the diethyl-nitrosamine (DEN)-induced HCC mouse model. As expected, expression of IL-22, an important factor involved in HCC progression, was markedly reduced by metformin. Treatment of HCC cells with metformin inhibited IL-22 induced cell proliferation, migration and invasion, and promoted cell apoptosis. Furthermore, ectopic expression of IL-22 makes HCC more aggressive whereas metformin largely compromised it in vitro and in vivo. Mechanistically, the whole transcriptome analysis and functional analysis revealed that Hippo signaling pathway was involved in the anti-tumor ability of metformin. Consistent with this, metformin directly activated Mst1/2, phosphorylated YAP1 in vitro. After blocking Hippo pathway by XMU-MP-1, the inhibitor of MST1/2, the inhibitory effects by metformin were dramatically attenuated as shown by in vitro study. Conclusions: Collectively, our findings illuminate a new regulatory mechanism, metformin activates Hippo signaling pathway to regulate IL-22 mediated HCC progression and provide new insights into its tumor-suppressive roles.

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