Functions of Yes-association protein (YAP) in cancer progression and anticancer therapy resistance

Wang, Xiang; Zhou, Xiuping

doi:10.26599/bsa.2022.9050008

Cited by 7 publications

(4 citation statements)

References 162 publications

(221 reference statements)

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“…The Hippo pathway is one of multiple pathways that regulate tissue development and carcinogenesis. Dysregulation of this pathway plays a vital role in the progression of numerous types of human cancers 15 . MiRNAs are essential for several biological processes because they regulate the expression of post-transcriptional genes.…”

Section: Discussionmentioning

confidence: 99%

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The possible correlation between miR-762, Hippo signaling pathway, TWIST1, and SMAD3 in lung cancer and chronic inflammatory diseases

Hussein,

Ebid,

Ahmad

et al. 2024

Sci Rep

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MicroRNAs are small RNA molecules that have a significant role in translational repression and gene silencing through binding to downstream target mRNAs. MiR-762 can stimulate the proliferation and metastasis of various types of cancer. Hippo pathway is one of the pathways that regulate tissue development and carcinogenesis. Dysregulation of this pathway plays a vital role in the progression of cancer. This study aimed to evaluate the possible correlation between miR-762, the Hippo signaling pathway, TWIST1, and SMAD3 in patients with lung cancer, as well as patients with chronic inflammatory diseases. The relative expression of miR-762, MST1, LATS2, YAP, TWIST1, and SMAD3 was determined in 50 lung cancer patients, 30 patients with chronic inflammatory diseases, and 20 healthy volunteers by real-time PCR. The levels of YAP protein and neuron-specific enolase were estimated by ELISA and electrochemiluminescence immunoassay, respectively. Compared to the control group, miR-762, YAP, TWIST1, and SMAD3 expression were significantly upregulated in lung cancer patients and chronic inflammatory patients, except SMAD3 was significantly downregulated in chronic inflammatory patients. MST1, LATS2, and YAP protein were significantly downregulated in all patients. MiR-762 has a significant negative correlation with MST1, LATS2, and YAP protein in lung cancer patients and with MST1 and LATS2 in chronic inflammatory patients. MiR-762 may be involved in the induction of malignant behaviors in lung cancer through suppression of the Hippo pathway. MiR-762, MST1, LATS2, YAP mRNA and protein, TWIST1, and SMAD3 may be effective diagnostic biomarkers in both lung cancer patients and chronic inflammatory patients. High YAP, TWIST1, SMA3 expression, and NSE level are associated with a favorable prognosis for lung cancer.

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Section: Discussionmentioning

confidence: 99%

“…Inflammation is an adaptive reaction driven by stressful situations and plays a crucial role in cancer growth and progression 15 . The lung is continuously subjected to a variety of stresses, including air pollution, free radicals, and chemical irritants.…”

Section: Discussionmentioning

confidence: 99%

The possible correlation between miR-762, Hippo signaling pathway, TWIST1, and SMAD3 in lung cancer and chronic inflammatory diseases

Hussein,

Ebid,

Ahmad

et al. 2024

Sci Rep

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“…However, the prognosis of glioma patients remains poor because of the development of resistance to TMZ chemotherapy [ 65 ]. In recent years, the development of immunotherapy for cancer treatment has resulted in hope for glioma patients [ 66 , 67 ]. However, the distinctively immune-privileged microenvironment that is formed due to the intrinsic expression of immunosuppressive cytokines, such as PD-1, PD-L1, TGF-β and IL10, and the lack of antigen-presenting cells (APCs) in the CNS result in challenges for glioma patient prognosis.…”

Section: Discussionmentioning

confidence: 99%

HK3 stimulates immune cell infiltration to promote glioma deterioration

Li,

Wang

et al. 2023

Cancer Cell Int

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Background Glioma is the most common and lethal type of brain tumor, and it is characterized by unfavorable prognosis and high recurrence rates. The reprogramming of energy metabolism and an immunosuppressive tumor microenvironment (TME) are two hallmarks of tumors. Complex and dynamic interactions between neoplastic cells and the surrounding microenvironment can generate an immunosuppressive TME, which can accelerate the malignant progression of glioma. Therefore, it is crucial to explore associations between energy metabolism and the immunosuppressive TME and to identify new biomarkers for glioma prognosis. Methods In our work, we analyzed the co-expression relationship between glycolytic genes and immune checkpoints based on the transcriptomic data from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) and found the correlation between HK3 expression and glioma tumor immune status. To investigate the biological role of HK3 in glioma, we performed bioinformatics analysis and established a mouse glioblastoma (GBM) xenograft model. Results Our study showed that HK3 significantly stimulated immune cell infiltration into the glioma TME. Tissue samples with higher HK3 expressive level showed increasing levels of immune cells infiltration, including M2 macrophages, neutrophils, and various subtypes of activated memory CD4+ T cells. Furthermore, HK3 expression was significantly increasing along with the elevated tumor grade, had a higher level in the mesenchymal subtype compared with those in other subtypes of GBM and could independently predict poor outcomes of GBM patients. Conclusion The present work mainly concentrated on the biological role of HK3 in glioma and offered a novel insight of HK3 regulating the activation of immune cells in the glioma microenvironment. These findings could provide a new theoretical evidence for understanding the metabolic molecular within the glioma microenvironment and identifying new therapeutic targets.

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“…Yes-associated protein (YAP) is a central effector of the hippo kinase cascade and usually plays an important role in the cancer-promoting process of most human tumors [ 15 , 16 , 17 , 18 ]. When the hippo kinase cascade is turned off, YAP enters the nucleus and interacts with the TEA structural domain (TEAD) family of transcription factors, leading to downstream target gene expression and tumor growth [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

SU4312 Represses Glioma Progression by Inhibiting YAP and Inducing Sensitization to the Effect of Temozolomide

Wang

Zhou

Wang

et al. 2022

JCM

Self Cite

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SU4312, initially designed as a multi-target tyrosine kinase inhibitor, is consequently reported to inhibit tumor angiogenesis by blocking VEGFR. However, although SU4312 can penetrate the brain–blood barrier, its potential to inhibit glioma growth is unknown. In this study, we report that SU4312 inhibited glioma cell proliferation and down-regulated yes-associated protein (YAP), the key effector of the hippo pathway. The exogenous over-expression of YAP partially restored the inhibitory effect of SU4312 on glioma progression. Interestingly, SU4312 sensitized the antitumor effect of temozolomide, both in vitro and in vivo. Moreover, SU4312 decreased the M2tumor-associated macrophages and enhanced anti-tumor immunity by down-regulating the YAP-CCL2 axis. In conclusion, our results suggest that SU4312 represses glioma progression by down-regulating YAP transcription and consequently CCL2 secretion. SU4312 may be synergistic with temozolomide for glioma treatment.

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Functions of Yes-association protein (YAP) in cancer progression and anticancer therapy resistance

Cited by 7 publications

References 162 publications

The possible correlation between miR-762, Hippo signaling pathway, TWIST1, and SMAD3 in lung cancer and chronic inflammatory diseases

The possible correlation between miR-762, Hippo signaling pathway, TWIST1, and SMAD3 in lung cancer and chronic inflammatory diseases

HK3 stimulates immune cell infiltration to promote glioma deterioration

SU4312 Represses Glioma Progression by Inhibiting YAP and Inducing Sensitization to the Effect of Temozolomide

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