<b>Kinase joins the chaperone club: Androgen-regulated kinome reveals choline kinase alpha as a potential drug target in prostate cancer</b>

Asim, Mohammad; Massie, Charles E.; Neal, David E.

doi:10.1080/23723556.2016.1140262

Cited by 5 publications

(6 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Paraffin-embedded tissues were used to perform immunohistochemical staining to detect AR and Ki67. The methodology to detect AR [14] and Ki67 [15] were detected as described earlier, respectively. A pre-validated anti-PBK (Sigma HPA0055753, 1:250 dilution) was used.…”

Section: Methodsmentioning

confidence: 99%

“…In addition to direct changes to the AR, another mechanism underlying CRPC growth is increased activity and/or expression of AR co-activators [12–14]. Yet another hallmark of AR signalling in PrCa is the integrated feed-forward and feedback circuits that facilitate pro-growth signalling as exemplified by the reciprocal positive feedback between AR and choline kinase alpha signalling [14, 15] and reciprocal negative feedback between AR and poly ADP-Ribose polymerase-1 signalling [16]. Androgens can also negatively regulate AR mRNA expression by recruitment of AR to a repressive element in intron 2 of the AR gene [17, 18].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A reciprocal feedback between the PDZ binding kinase and androgen receptor drives prostate cancer

et al. 2018

Self Cite

View full text Add to dashboard Cite

Elucidation of mechanisms underlying the increased androgen receptor (AR) activity and subsequent development of aggressive prostate cancer (PrCa) is pivotal in developing new therapies. Using a systems biology approach, we interrogated the AR-regulated proteome and identified PDZ binding kinase (PBK) as a novel AR-regulated protein that regulates full-length AR and AR variants (ARVs) activity in PrCa. PBK overexpression in aggressive PrCa is associated with early biochemical relapse and poor clinical outcome. In addition to its carboxy terminus ligand-binding domain, PBK directly interacts with the amino terminus transactivation domain of the AR to stabilise it thereby leading to increased AR protein expression observed in PrCa. Transcriptome sequencing revealed that PBK is a mediator of global AR signalling with key roles in regulating tumour invasion and metastasis. PBK inhibition decreased growth of PrCa cell lines and clinical specimen cultured ex vivo. We uncovered a novel interplay between AR and PBK that results in increased AR and ARVs expression that executes AR-mediated growth and progression of PrCa, with implications for the development of PBK inhibitors for the treatment of aggressive PrCa.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A reciprocal feedback between the PDZ binding kinase and androgen receptor drives prostate cancer

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…In keeping with this, a balance between ChoKα and ChoKβ may be required for the appropriate regulation of cell proliferation and reduction of the protein levels of ChoKα may be required in some cell systems for induction of cell death [19]. Furthermore, a chaperone activity has been reported for ChoKα [86,87]. If this is correct, effective ChoKαIs must be able to simultaneously reduce ChoKα enzymatic activity and intracellular protein levels.…”

Section: Chokis Mechanism Of Actionmentioning

confidence: 99%

Choline Kinase: An Unexpected Journey for a Precision Medicine Strategy in Human Diseases

Lacal

Zimmerman²,

Campos

2021

Pharmaceutics

View full text Add to dashboard Cite

Choline kinase (ChoK) is a cytosolic enzyme that catalyzes the phosphorylation of choline to form phosphorylcholine (PCho) in the presence of ATP and magnesium. ChoK is required for the synthesis of key membrane phospholipids and is involved in malignant transformation in a large variety of human tumours. Active compounds against ChoK have been identified and proposed as antitumor agents. The ChoK inhibitory and antiproliferative activities of symmetrical bispyridinium and bisquinolinium compounds have been defined using quantitative structure–activity relationships (QSARs) and structural parameters. The design strategy followed in the development of the most active molecules is presented. The selective anticancer activity of these structures is also described. One promising anticancer compound has even entered clinical trials. Recently, ChoKα inhibitors have also been proposed as a novel therapeutic approach against parasites, rheumatoid arthritis, inflammatory processes, and pathogenic bacteria. The evidence for ChoKα as a novel drug target for approaches in precision medicine is discussed.

show abstract

“…Many tumors display altered lipid metabolism during development and as a consequence of chemotherapy CK is upregulated in many tumors and is associated with various malignant phenotypes . Furthermore, CK was recently reported as an androgen receptor chaperone and potentially valuable drug target in prostate cancer . TCD 717 is the first CK inhibitor to have recently entered clinical trials in solid tumors (Table S29).…”

Section: Approved and Experimental Kinase Inhibitor Drugsmentioning

confidence: 99%

Approved and Experimental Small‐Molecule Oncology Kinase Inhibitor Drugs: A Mid‐2016 Overview

Fischer

2016

Medicinal Research Reviews

View full text Add to dashboard Cite

Kinase joins the chaperone club: Androgen-regulated kinome reveals choline kinase alpha as a potential drug target in prostate cancer

Cited by 5 publications

References 7 publications

A reciprocal feedback between the PDZ binding kinase and androgen receptor drives prostate cancer

A reciprocal feedback between the PDZ binding kinase and androgen receptor drives prostate cancer

Choline Kinase: An Unexpected Journey for a Precision Medicine Strategy in Human Diseases

Approved and Experimental Small‐Molecule Oncology Kinase Inhibitor Drugs: A Mid‐2016 Overview

Contact Info

Product

Resources

About