ADNP Upregulation Promotes Bladder Cancer Cell Proliferation via the AKT Pathway

Zhu, Sipin; Xu, Zhongzhi; Zeng, Yong; Long, Ying; Fan, Gang; Ding, Qi; Yang, Wen; Cao, Jun; Dai, Tao; Wang, Han; Xie, Yu

doi:10.3389/fonc.2020.491129

Cited by 12 publications

(12 citation statements)

References 43 publications

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“…Transcriptional assessment of ADNP levels in a large cohort of bladder cancer specimens highlighted a significant overexpression in the patients with tumor progression and the association of higher ADNP protein levels to poor prognosis in such patients [ 161 ]. In bladder cancer, ADNP promotes tumor cell growth and proliferation by enhancing the AKT-MDM2-p53 molecular axis which stabilizes cyclin D1 and ultimately leads to cell cycle acceleration from G1 phase to S phase [ 162 ]. In another study, ADNP was found to promote bladder cancer cell migration via TGF- β -mediated epithelial-mesenchymal transition (EMT) pathway [ 161 ].…”

Section: Adnp Dysregulation In Cancer Developmentmentioning

confidence: 99%

Chromatin remodeler Activity-Dependent Neuroprotective Protein (ADNP) contributes to syndromic autism

et al. 2023

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Background Individuals affected with autism often suffer additional co-morbidities such as intellectual disability. The genes contributing to autism cluster on a relatively limited number of cellular pathways, including chromatin remodeling. However, limited information is available on how mutations in single genes can result in such pleiotropic clinical features in affected individuals. In this review, we summarize available information on one of the most frequently mutated genes in syndromic autism the Activity-Dependent Neuroprotective Protein (ADNP). Results Heterozygous and predicted loss-of-function ADNP mutations in individuals inevitably result in the clinical presentation with the Helsmoortel–Van der Aa syndrome, a frequent form of syndromic autism. ADNP, a zinc finger DNA-binding protein has a role in chromatin remodeling: The protein is associated with the pericentromeric protein HP1, the SWI/SNF core complex protein BRG1, and other members of this chromatin remodeling complex and, in murine stem cells, with the chromodomain helicase CHD4 in a ChAHP complex. ADNP has recently been shown to possess R-loop processing activity. In addition, many additional functions, for instance, in association with cytoskeletal proteins have been linked to ADNP. Conclusions We here present an integrated evaluation of all current aspects of gene function and evaluate how abnormalities in chromatin remodeling might relate to the pleiotropic clinical presentation in individual“s” with Helsmoortel–Van der Aa syndrome.

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Section: Adnp Dysregulation In Cancer Developmentmentioning

confidence: 99%

Chromatin remodeler Activity-Dependent Neuroprotective Protein (ADNP) contributes to syndromic autism

et al. 2023

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“…At a molecular level, ADNP was found to activate the AKT/ MDM2 / p53 signaling pathway, thus promoting bladder cancer cell proliferation. Taken together, ADNP is overexpressed in bladder cancer and may act as an oncogene in bladder tumorigenesis [ 137 ]. Hence, ADNP may be a novel molecular target for predicting prognosis in bladder cancer as well as adjuvant therapeutic for bladder cancer patients receiving intravesical chemotherapy.…”

Section: Homeobox Genes In Bladder Cancermentioning

confidence: 99%

Homeobox Gene Expression Dysregulation as Potential Diagnostic and Prognostic Biomarkers in Bladder Cancer

2023

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Homeobox genes serve as master regulatory transcription factors that regulate gene expression during embryogenesis. A homeobox gene may have either tumor-promoting or tumor-suppressive properties depending on the specific organ or cell lineage where it is expressed. The dysregulation of homeobox genes has been reported in various human cancers, including bladder cancer. The dysregulated expression of homeobox genes has been associated with bladder cancer clinical outcomes. Although bladder cancer has high risk of tumor recurrence and progression, it is highly challenging for clinicians to accurately predict the risk of tumor recurrence and progression at the initial point of diagnosis. Cystoscopy is the routine surveillance method used to detect tumor recurrence. However, the procedure causes significant discomfort and pain that results in poor surveillance follow-up amongst patients. Therefore, the development of reliable non-invasive biomarkers for the early detection and monitoring of bladder cancer is crucial. This review provides a comprehensive overview of the diagnostic and prognostic potential of homeobox gene expression dysregulation in bladder cancer.

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“…However, the activation of ADNP signaling system, mediated by an endogenous pituitary adenylate cyclase-activating polypeptide, can increase the resistance of malignant peripheral nerve sheath tumor to H2O2-induced death with serum starvation [16]. Our previous study has shown that overexpression of ADNP in BC stimulated the Akt-MDM2-p53 pathway and enhanced binding of cyclin D1 to CDK4 or CDK6, accelerating the cell cycle transition from G1 phase to S phase [17]. ADNP may act as an oncogene in certain cellular contexts.…”

Section: Ivyspringmentioning

confidence: 99%

ADNP prompts the cisplatin-resistance of bladder cancer via TGF-β-mediated epithelial-mesenchymal transition (EMT) pathway

Xie¹,

Zhu²,

Zang³

et al. 2021

J. Cancer

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Activity-dependent neuroprotective protein (ADNP) is vital for embryonic development and brain formation. Besides, the upregulated expression of ADNP enhances tumorigenesis in some human tumors like bladder cancer (BC). However, the potential roles of ADNP in drug resistance and the related mechanisms in BC is unknown. We performed this study to elucidate the influence of ADNP in the chemoresistance of BC and tried to explore the underlying molecular mechanism. The expressions of ADNP in BC from progression and non-progression patient specimens were measured by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). In vitro experiments including colony formation, cell counting kit-8 (CCK-8), wound healing, and in vivo tumorigenesis assay were performed to explore the effects of ADNP on chemoresistance of BC. The impacts of ADNP on TGF-β/Smad signaling pathways were explored by western blot. Our results showed that the expression of ADNP mRNA and protein were significantly upregulated in BC tissues of the patients who suffered tumor-progression via RT-PCR and western blot. Cox regression survival analysis revealed that patients with high ADNP expression closely linked to shorter tumor-free survival. ADNP downregulation in BC showed more sensitive to cisplatin in vivo, while ADNP overexpression showed the opposite results. Additionally, we confirmed that ADNP promoted cell migration and EMT, thereby inducing cisplatin resistance, which may be related to TGF-β / Smad signaling pathway.

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ADNP Upregulation Promotes Bladder Cancer Cell Proliferation via the AKT Pathway

Cited by 12 publications

References 43 publications

Chromatin remodeler Activity-Dependent Neuroprotective Protein (ADNP) contributes to syndromic autism

Chromatin remodeler Activity-Dependent Neuroprotective Protein (ADNP) contributes to syndromic autism

Homeobox Gene Expression Dysregulation as Potential Diagnostic and Prognostic Biomarkers in Bladder Cancer

ADNP prompts the cisplatin-resistance of bladder cancer via TGF-β-mediated epithelial-mesenchymal transition (EMT) pathway

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