Expression of protein kinase A regulatory subunits in benign and malignant human thyroid tissues: A systematic review

Gobbo, Alessandro Del; Peverelli, Erika; Treppiedi, Donatella; Lania, Andrea; Mantovani, Giovanna; Ferrero, Stefano

doi:10.1016/j.yexcr.2016.06.004

Cited by 7 publications

(3 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar result is also observed in liver cancer cells, where PKA directly phosphorylates AMPK to reverse the cell cycle arrest [73]. Clinically, both regulatory subunits of PKA are overexpressed in thyroid carcinoma, correlating with stronger motility and proliferative ability [74]. …”

Section: Functions Of Ampk Signaling Components In Tumorigenesissupporting

confidence: 53%

Functional characterization of AMP-activated protein kinase signaling in tumorigenesis

Cheng

Zhang

et al. 2016

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

View full text Add to dashboard Cite

AMP-activated protein kinase (AMPK) is a ubiquitously expressed metabolic sensor among various species. Specifically, cellular AMPK is phosphorylated and activated under certain stressful conditions, such as energy deprivation, in turn to activate diversified downstream substrates to modulate the adaptive changes and maintain metabolic homeostasis. Recently, emerging evidences have implicated the potential roles of AMPK signaling in tumor initiation and progression. Nevertheless, a comprehensive description on such topic is still in scarcity, especially in combination of its biochemical features with mouse modeling results to elucidate the physiological role of AMPK signaling in tumorigenesis. Hence, we performed this thorough review by summarizing the tumorigenic role of each component along the AMPK signaling, comprising of both its upstream and downstream effectors. Moreover, their functional interplay with the AMPK heterotrimer and exclusive efficacies in carcinogenesis were chiefly explained among genetically altered mice models. Importantly, the pharmaceutical investigations of AMPK relevant medications have also been highlighted. In summary, in this review, we not only elucidate the potential functions of AMPK signaling pathway in governing tumorigenesis, but also potentiate the future targeted strategy aiming for better treatment of aberrant metabolism-associated diseases, including cancer.

show abstract

Section: Functions Of Ampk Signaling Components In Tumorigenesissupporting

confidence: 53%

Functional characterization of AMP-activated protein kinase signaling in tumorigenesis

Cheng

Zhang

et al. 2016

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

View full text Add to dashboard Cite

show abstract

“…The cyclic nucleotide second messengers, cAMP and cGMP, activate PKA, PKG1, and PKG2. PKA and cAMP seem to protect thyroid cells from apoptosis and support a contribution of p70S6K to viability [ 39 , 40 , 41 , 42 , 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Differentiating Benign from Malignant Thyroid Tumors by Kinase Activity Profiling and Dabrafenib BRAF V600E Targeting

Hilhorst,

van den Berg,

Boender

et al. 2023

Cancers

View full text Add to dashboard Cite

Differentiated non-medullary thyroid cancer (NMTC) can be effectively treated by surgery followed by radioactive iodide therapy. However, a small subset of patients shows recurrence due to a loss of iodide transport, a phenotype frequently associated with BRAF V600E mutations. In theory, this should enable the use of existing targeted therapies specifically designed for BRAF V600E mutations. However, in practice, generic or specific drugs aimed at molecular targets identified by next generation sequencing (NGS) are not always beneficial. Detailed kinase profiling may provide additional information to help improve therapy success rates. In this study, we therefore investigated whether serine/threonine kinase (STK) activity profiling can accurately classify benign thyroid lesions and NMTC. We also determined whether dabrafenib (BRAF V600E-specific inhibitor), as well as sorafenib and regorafenib (RAF inhibitors), can differentiate BRAF V600E from non-BRAF V600E thyroid tumors. Using 21 benign and 34 malignant frozen thyroid tumor samples, we analyzed serine/threonine kinase activity using PamChip®peptide microarrays. An STK kinase activity classifier successfully differentiated malignant (26/34; 76%) from benign tumors (16/21; 76%). Of the kinases analyzed, PKC (theta) and PKD1 in particular, showed differential activity in benign and malignant tumors, while oncocytic neoplasia or Graves’ disease contributed to erroneous classifications. Ex vivo BRAF V600E-specific dabrafenib kinase inhibition identified 6/92 analyzed peptides, capable of differentiating BRAF V600E-mutant from non-BRAF V600E papillary thyroid cancers (PTCs), an effect not seen with the generic inhibitors sorafenib and regorafenib. In conclusion, STK activity profiling differentiates benign from malignant thyroid tumors and generates unbiased hypotheses regarding differentially active kinases. This approach can serve as a model to select novel kinase inhibitors based on tissue analysis of recurrent thyroid and other cancers.

show abstract

“…Since that time cAMP signalling has been shown to transactivate the androgen receptor, regulate androgen sensitive transcription and underpin neuroendocrine differentiation in the prostate. Furthermore, the principle cAMP effector proteins, namely protein kinase A (PKA) [35][36][37] and EPAC1/2 [38], have been directly implicated in aberrant molecular signalling pathways that support the growth of cancerous lesions.…”

Section: Camp and Prostate Cancermentioning

confidence: 99%

Creating a potential diagnostic for prostate cancer risk stratification (InformMDx™) by translating novel scientific discoveries concerning cAMP degrading phosphodiesterase-4D7 (PDE4D7)

et al. 2019

View full text Add to dashboard Cite

Increased PSA-based screening for prostate cancer has resulted in a growing number of diagnosed cases. However, around half of these are ‘indolent’, neither metastasizing nor leading to disease specific death. Treating non-progressing tumours with invasive therapies is currently regarded as unnecessary over-treatment with patients being considered for conservative regimens, such as active surveillance (AS). However, this raises both compliance and protocol issues. Great clinical benefit could accrue from a biomarker able to predict long-term patient outcome accurately at the time of biopsy and initial diagnosis. Here we delineate the translation of a laboratory discovery through to the precision development of a clinically validated, novel prognostic biomarker assay (InformMDx™). This centres on determining transcript levels for phosphodiesterase-4D7 (PDE4D7), an enzyme that breaks down cyclic AMP, a signalling molecule intimately connected with proliferation and androgen receptor function. Quantifiable detection of PDE4D7 mRNA transcripts informs on the longitudinal outcome of post-surgical disease progression. The risk of post-surgical progression increases steeply for patients with very low ‘PDE4D7 scores’, while risk decreases markedly for those patients with very high ‘PDE4D7 scores’. Combining clinical risk variables, such as the Gleason or CAPRA (Cancer of the Prostate Risk Assessment) score, with the ‘PDE4D7 score’ further enhances the prognostic power of this personalized, precision assessment. Thus the ‘PDE4D7 score’ has the potential to define, more effectively, appropriate medical intervention/AS strategies for individual prostate cancer patients.

show abstract

Expression of protein kinase A regulatory subunits in benign and malignant human thyroid tissues: A systematic review

Cited by 7 publications

References 38 publications

Functional characterization of AMP-activated protein kinase signaling in tumorigenesis

Functional characterization of AMP-activated protein kinase signaling in tumorigenesis

Differentiating Benign from Malignant Thyroid Tumors by Kinase Activity Profiling and Dabrafenib BRAF V600E Targeting

Creating a potential diagnostic for prostate cancer risk stratification (InformMDx™) by translating novel scientific discoveries concerning cAMP degrading phosphodiesterase-4D7 (PDE4D7)

Contact Info

Product

Resources

About