POPDC proteins as potential novel therapeutic targets in cancer

Amunjela, Johanna Ndamwena; Tucker, Steven

doi:10.1016/j.drudis.2016.07.011

Cited by 18 publications

(22 citation statements)

References 72 publications

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“…POPDC1 is found both at the nuclear envelope and in some cell types also in the nucleosplasm. The nuclear localization has been reported in various cell lines including cardiac myocytes, myoblasts and epithelial breast cancer cells [2,9,36]. Furthermore, similar nuclear expression patterns have also been observed in the case of POPDC2 and POPDC3 [36,59,60].…”

Section: Nuclear Localization and The Interaction With Zonula Occludesupporting

confidence: 54%

“…The Popeye domain containing (POPDC) proteins are a novel class of cAMP binding, transmembrane proteins. The POPDC gene family consists of three isoforms: POPDC1, POPDC2 and POPDC3 [2,4,9]. POPDC1, also known as blood vessel epicardial substance (BVES), was first discovered 20 years ago.…”

Section: The Popdc Protein Familymentioning

confidence: 99%

“…The structure of POPDC proteins consists of a short (27-39 residues) extracellular amino terminus followed by three transmembrane domains, a cytoplasmic Popeye domain and the carboxyl terminal domain (CTD), which is of variable length and the sequence is isoform-specific [2,7] (Figure 1). The protein is tethered to the plasma membrane as a dimer that in the case of POPDC1 is stabilized by a disulfide bridge.…”

Section: The Popdc Protein Familymentioning

confidence: 99%

“…Cyclic adenosine monophosphate (cAMP) is a second messenger that relays cellular signals downstream of G-protein coupled receptors (GPCRs), to regulate multiple targets that trigger cellular responses to various ligands [1][2][3]. Signaling of the cAMP pathway is initiated when a ligand binds to its binding site on a G-protein coupled receptor (GPCR) causing the activation of G α s. G α s stimulates adenylyl cyclase (AC), which converts adenosine triphosphate (ATP) to cAMP [2,4]. At elevated…”

Section: Introductionmentioning

confidence: 99%

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The Role of the Popeye Domain Containing Gene Family in Organ Homeostasis

Amunjela

Swan

Brand

2019

Cells

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The Popeye domain containing (POPDC) gene family consists of POPDC1 (also known as BVES), POPDC2 and POPDC3 and encodes a novel class of cyclic adenosine monophosphate (cAMP) effector proteins. Despite first reports of their isolation and initial characterization at the protein level dating back 20 years, only recently major advances in defining their biological functions and disease association have been made. Loss-of-function experiments in mice and zebrafish established an important role in skeletal muscle regeneration, heart rhythm control and stress signaling. Patients suffering from muscular dystrophy and atrioventricular block were found to carry missense and nonsense mutations in either of the three POPDC genes, which suggests an important function in the control of striated muscle homeostasis. However, POPDC genes are also expressed in a number of epithelial cells and function as tumor suppressor genes involved in the control of epithelial structure, tight junction formation and signaling. Suppression of POPDC genes enhances tumor cell proliferation, migration, invasion and metastasis in a variety of human cancers, thus promoting a malignant phenotype. Moreover, downregulation of POPDC1 and POPDC3 expression in different cancer types has been associated with poor prognosis. However, high POPDC3 expression has also been correlated to poor clinical prognosis in head and neck squamous cell carcinoma, suggesting that POPDC3 potentially plays different roles in the progression of different types of cancer. Interestingly, a gain of POPDC1 function in tumor cells inhibits cell proliferation, migration and invasion thereby reducing malignancy. Furthermore, POPDC proteins have been implicated in the control of cell cycle genes and epidermal growth factor and Wnt signaling. Work in tumor cell lines suggest that cyclic nucleotide binding may also be important in epithelial cells. Thus, POPDC proteins have a prominent role in tissue homeostasis and cellular signaling in both epithelia and striated muscle.

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Section: Nuclear Localization and The Interaction With Zonula Occludesupporting

confidence: 54%

Section: The Popdc Protein Familymentioning

confidence: 99%

Section: The Popdc Protein Familymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Role of the Popeye Domain Containing Gene Family in Organ Homeostasis

Amunjela

Swan

Brand

2019

Cells

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“…In addition, loss of POPDC1 has been shown to promote colorectal cancer tumorigenesis via activation of c-Myc regulated networks and activation of Wnt signalling [ 12 ]. Although the exact functional mechanisms of POPDC1 are poorly understood, the known roles and correlations between POPDC1 with cancer and cardiovascular diseases have been recently reviewed [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of POPDC1 promotes breast cancer cell migration and proliferation

Amunjela

Tucker

2017

Bioscience Reports

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Breast cancer subtypes such as triple-negative that lack the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 receptor (HER2), remain poorly clinically managed due to a lack of therapeutic targets. This necessitates identification and validation of novel targets. Suppression of Popeye domain-containing protein 1 (POPDC1) is known to promote tumorigenesis and correlate to poor clinical outcomes in various cancers, and also promotes cardiac and skeletal muscle pathologies. It remains to be established whether POPDC1 is dysregulated in breast cancer, and whether overcoming the dysregulation of POPDC1 could present a potential therapeutic strategy to inhibit breast tumorigenesis. We assessed the potential of POPDC1 as a novel target for inhibiting breast cancer cell migration and proliferation. POPDC1 was significantly suppressed with reduced cell membrane localization in breast cancer cells. Furthermore, functional suppression of POPDC1 promoted breast cancer cell migration and proliferation, which were inhibited by POPDC1 overexpression. Finally, cAMP interacts with POPDC1 and up-regulates its expression in breast cancer cells. These findings suggest that POPDC1 plays a role in breast tumorigenesis and represents a potential therapeutic target or biomarker in breast cancer medicine.

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Identification of hub genes in bladder cancer based on weighted gene co‐expression network analysis from TCGA database

Wang

Miao

et al. 2021

Cancer Reports

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Background Muscular invasive bladder cancer (MIBC) is a common malignant tumor in the world. Because of their heterogeneity in prognosis and response to treatment, biomarkers that can predict survival or help make treatment decisions in patients with MIBC are essential for individualized treatment. Aim We aimed to integrate bioinformatics research methods to identify a set of effective biomarkers capable of predicting, diagnosing, and treating MIBC. To provide a new theoretical basis for the diagnosis and treatment of bladder cancer. Methods and results Gene expression profiles and clinical data of MIBC were obtained by downloading from the Cancer Genome Atlas database. A dataset of 129 MIBC cases and controls was included. 2084 up‐regulated genes and 2961 down‐regulated genes were identified by differentially expressed gene (DEG) analysis. Then, gene ontology analysis was performed to explore the biological functions of DEGs, respectively. The up‐regulated DEGs are mainly enriched in epidermal cell differentiation, mitotic nuclear division, and so forth. They are also involved in the cell cycle, p53 signaling pathway, PPAR signaling pathway, and so forth. The weighted gene co‐expression network analysis yielded five modules related to pathological stages and grading, of which blue and turquoise were the most relevant modules for MIBC. Next, Using Kaplan–Meier survival analysis to identify further hub genes, the screening criteria at p ≤ .05, we found CNKSR1 , HIP1R , CFL2 , TPM1 , CSRP1 , SYNM , POPDC2 , PJA2 , and RBBP8NL genes associated with the progression and prognosis of MIBC patients. Finally, immunohistochemistry experiments further confirmed that CNKSR1 plays a vital role in the tumorigenic context of MIBC. Conclusion The research suggests that CNKSR1 , POPDC2 , and PJA2 may be novel biomarkers as therapeutic targets for MIBC, especially we used immunohistochemical further to validate CNKSR1 as a therapeutic target for MIBC which may help to improve the prognosis for MIBC.

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POPDC proteins as potential novel therapeutic targets in cancer

Cited by 18 publications

References 72 publications

The Role of the Popeye Domain Containing Gene Family in Organ Homeostasis

The Role of the Popeye Domain Containing Gene Family in Organ Homeostasis

Dysregulation of POPDC1 promotes breast cancer cell migration and proliferation

Identification of hub genes in bladder cancer based on weighted gene co‐expression network analysis from TCGA database

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