How does YAP protein regulate the androgen signaling pathway in prostate cancer?

1. What are the clinical challenges in prostate cancer treatment?

Prostate cancer, as a highly prevalent malignant tumor in males, has androgen receptor-positive subtypes accounting for approximately 90% of all cases. The androgen receptor signaling pathway plays a central regulatory role in tumorigenesis and progression by activating downstream gene transcription to promote tumor growth. Although new-generation androgen receptor antagonists such as enzalutamide have significantly improved treatment efficacy, endocrine therapy resistance remains a major clinical challenge.

Studies on resistance mechanisms reveal that androgen receptor gene amplification and the generation of splice variants are important factors leading to treatment failure. These variants often lose drug-binding sites, resulting in sustained activation of the signaling pathway. Therefore, in-depth analysis of the androgen signaling pathway's regulatory network and discovery of new intervention targets hold significant clinical importance for overcoming drug resistance and improving patient prognosis.

2. What is the application value of Phospho-YAP recombinant rabbit monoclonal antibody in related research?

The Phospho-YAP recombinant rabbit monoclonal antibody, as a research tool specifically recognizing phosphorylated YAP protein, holds significant value in prostate cancer mechanism studies and therapeutic development. This antibody is prepared by immunizing New Zealand White rabbits, exhibiting high affinity and specificity, enabling accurate detection of YAP protein phosphorylation states at different sites.

In signaling pathway research, this antibody can be used for Western blot analysis to quantitatively detect changes in YAP phosphorylation levels under the action of MST1/2 and LATS1/2 kinases. By comparing YAP phosphorylation states under different treatment conditions, Hippo pathway activity characteristics in prostate cancer can be evaluated. Immunofluorescence techniques combined with this antibody can visualize YAP distribution changes between cytoplasm and nucleus, elucidating its nuclear translocation regulatory mechanisms.

In functional validation experiments, this antibody can be used to assess the impact of YAP activity regulation on androgen receptor signaling. By examining the correlation between YAP phosphorylation states and AR activity, the regulatory relationship between them can be deeply analyzed. Additionally, this antibody can be used for clinical sample analysis to explore the correlation between YAP phosphorylation states and prostate cancer progression and treatment response.

3. What regulatory role does YAP play in prostate cancer?

Unlike its pro-cancer role in most malignant tumors, studies have found that YAP exhibits unique regulatory characteristics in androgen receptor-positive prostate cancer. Clinical data analysis shows that YAP expression levels in prostate cancer tissues are lower than in normal prostate tissues, and its high expression is associated with favorable prognosis. This phenomenon suggests YAP may function as a tumor suppressor gene in prostate cancer.

Functional experiments confirm that activating YAP through MST inhibitors or overexpressing phosphorylation site-mutated YAP5SA can inhibit prostate cancer growth in both in vivo and in vitro models. Transcriptomic analysis further reveals that YAP activation can inhibit androgen signaling pathway target gene expression at the whole-genome level. These findings uncover YAP's novel function in androgen signaling regulation, providing theoretical basis for its potential as a therapeutic target.

4. How does YAP regulate the androgen receptor signaling pathway?

Mechanistic studies reveal that YAP regulates androgen receptor signaling through competitive binding with transcription factor TEAD. Under normal physiological conditions, TEAD4 acts as a synergistic activator of androgen signaling, co-localizing with AR at numerous genomic sites to jointly promote downstream gene transcription. Chromatin immunoprecipitation sequencing analysis confirms the existence of this synergistic effect.

When YAP is activated, it enters the nucleus and binds to TEAD, competitively blocking TEAD-AR interaction. This competitive mechanism reduces AR's binding capacity at target gene enhancers and promoters, thereby inhibiting androgen signaling pathway transcriptional activity. Notably, this inhibitory mechanism is equally effective against both full-length AR and splice variants, offering new insights for addressing enzalutamide resistance.

5. Why does YAP exhibit different functions in different tumors?

Research finds that YAP can play diametrically opposite roles in different tumor types, with this "versatile" characteristic closely related to its context-dependent regulatory mechanisms. In most epithelial-derived tumors, YAP exerts pro-cancer effects by promoting cell proliferation and inhibiting apoptosis. However, in prostate cancer, specific breast cancer subtypes, and renal clear cell carcinoma, YAP demonstrates tumor-suppressive properties.

This functional divergence may relate to differences in transcriptional networks regulated by YAP across cellular environments. In prostate cancer, YAP primarily inhibits androgen signaling through competitive TEAD binding; in estrogen receptor-positive breast cancer, YAP suppresses tumor growth by blocking TEAD-estrogen receptor interaction; in renal clear cell carcinoma, YAP inhibits tumor progression by interfering with HIF2α-TEAD binding. These findings suggest YAP's functions exhibit high tissue specificity and context dependency.

6. What are the clinical implications of these findings?

This research provides new targeted strategies for prostate cancer treatment. Inhibiting androgen signaling through YAP activation may represent a novel approach to overcome enzalutamide resistance. Particularly in cases of AR splice variant-mediated resistance, YAP's regulatory mechanism remains effective, demonstrating unique therapeutic advantages.

Therapeutically, targeting the Hippo pathway may offer new intervention directions for prostate cancer. YAP activators like MST inhibitors show promising anti-tumor effects in preclinical studies, laying foundation for subsequent drug development. Meanwhile, YAP expression levels may serve as biomarkers for prostate cancer prognosis assessment and treatment response prediction.

7. Which manufacturers provide Phospho-YAP recombinant rabbit monoclonal antibodies?

Hangzhou Start Biotech Co., Ltd. has independently developed the "Phospho-YAP (Ser127) Recombinant Rabbit mAb" (Product Name: Phospho-YAP (Ser127) Recombinant Rabbit mAb (S-1364-28), Catalog Number: S0B1479), a high-performance research tool for detecting Hippo pathway core effector molecule activity with exceptional phosphorylation site specificity, sensitivity, and stability. This product, developed using recombinant rabbit monoclonal antibody technology, has been rigorously validated across multiple platforms including Western Blot (WB), Immunofluorescence (IF), and Immunohistochemistry (IHC), proving invaluable for Hippo pathway activity monitoring, contact inhibition studies, and tumorigenesis mechanism research.

Professional technical support: We provide comprehensive product documentation, including dynamic change examples under different cell densities or stimuli, nuclear-cytoplasmic ratio calculation methods when used with total YAP antibodies, and expert technical consultation, fully supporting customers in achieving precise, reliable discoveries in cell growth regulation and cancer biology research.

Hangzhou Start Biotech Co., Ltd. remains committed to providing high-quality, high-value biological reagents and solutions for global innovative pharmaceutical companies and research institutions. For more information about "Phospho-YAP (Ser127) Recombinant Rabbit mAb" (Catalog Number S0B1479) or sample testing requests, please contact us.

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