Heparanase and the hallmarks of cancer DOI Creative Commons

Krishnath M. Jayatilleke,

Mark D. Hulett

Journal of Translational Medicine, Journal Year: 2020, Volume and Issue: 18(1)

Published: Nov. 30, 2020

Abstract Heparanase is the only mammalian enzyme that cleaves heparan sulphate, an important component of extracellular matrix. This leads to remodelling matrix, whilst liberating growth factors and cytokines bound sulphate. in turn promotes both physiological pathological processes such as angiogenesis, immune cell migration, inflammation, wound healing metastasis. Furthermore, heparanase exhibits non-enzymatic actions signalling regulating gene expression. Cancer underpinned by key characteristic features promote malignant disease progression, collectively termed ‘hallmarks cancer’. Essentially, all cancers examined date have been reported overexpress heparanase, leading enhanced tumour metastasis with concomitant poor patient survival. With its multiple roles within microenvironment, has demonstrated regulate each these hallmark features, highlighting need for heparanase-targeted therapies. However, recent discoveries which can also vital anti-tumour mechanisms cast doubt on this approach. review will explore myriad ways functions a regulator hallmarks cancer highlight role major microenvironment. The dual however, emphasises further investigation into defining precise mechanism action different settings.

Language: Английский

A compendium of ERK targets DOI Open Access

Evrim B. Ünal,

Florian Uhlitz, Nils Blüthgen

et al.

FEBS Letters, Journal Year: 2017, Volume and Issue: 591(17), P. 2607 - 2615

Published: July 4, 2017

The RAF-MEK-ERK cascade is one of the most studied signaling pathways as it controls many vital cellular programs. There has been an immense amount effort to determine ERK target proteins involved in regulating these Classical biochemical and genetic approaches have elicited hundreds direct substrates, with advent phospho-proteomic technologies, numerous studies expanded number proteins. Here, we compile a comprehensive phospho-site archive, which gathered information from various research studies, provide this archive online database form searchable compendium targets.

Language: Английский

Citations

159
A Real-Time Biosensor for ERK Activity Reveals Signaling Dynamics during C. elegans Cell Fate Specification DOI Creative Commons
Claire de la Cova, Robert Townley, Sergi Regot

et al.

Developmental Cell, Journal Year: 2017, Volume and Issue: 42(5), P. 542 - 553.e4

Published: Aug. 17, 2017

Language: Английский

Citations

147
Phenotypic Plasticity, Bet-Hedging, and Androgen Independence in Prostate Cancer: Role of Non-Genetic Heterogeneity DOI Creative Commons
Mohit Kumar Jolly, Prakash Kulkarni,

Keith Weninger

et al.

Frontiers in Oncology, Journal Year: 2018, Volume and Issue: 8

Published: March 6, 2018

It is well known that genetic mutations can drive drug resistance and lead to tumor relapse. Here, we instead focus on alternate mechanisms – those without such as phenotypic plasticity stochastic cell-to-cell variability also evade attacks by giving rise drug-tolerant persisters. The phenomenon of persistence has been well-studied in bacteria recently garnered attention cancer. We draw a parallel between bacterial against androgen deprivation therapy prostate cancer (PCa), the primary standard care for metastatic disease. illustrate how consequent mutation-independent or non-genetic heterogeneity possibly driven protein conformational dynamics stochastically give independence PCa, suggest dynamic should be considered devising therapeutic dosing strategies designed treat manage PCa.

Language: Английский

Citations

138
The anti-cancer effects and mechanisms of lactic acid bacteria exopolysaccharides in vitro: A review DOI
Jiayi Wu, Yuheng Zhang, Ling Ye

et al.

Carbohydrate Polymers, Journal Year: 2020, Volume and Issue: 253, P. 117308 - 117308

Published: Oct. 24, 2020

Language: Английский

Citations

134
Heparanase and the hallmarks of cancer DOI Creative Commons

Krishnath M. Jayatilleke,

Mark D. Hulett

Journal of Translational Medicine, Journal Year: 2020, Volume and Issue: 18(1)

Published: Nov. 30, 2020

Abstract Heparanase is the only mammalian enzyme that cleaves heparan sulphate, an important component of extracellular matrix. This leads to remodelling matrix, whilst liberating growth factors and cytokines bound sulphate. in turn promotes both physiological pathological processes such as angiogenesis, immune cell migration, inflammation, wound healing metastasis. Furthermore, heparanase exhibits non-enzymatic actions signalling regulating gene expression. Cancer underpinned by key characteristic features promote malignant disease progression, collectively termed ‘hallmarks cancer’. Essentially, all cancers examined date have been reported overexpress heparanase, leading enhanced tumour metastasis with concomitant poor patient survival. With its multiple roles within microenvironment, has demonstrated regulate each these hallmark features, highlighting need for heparanase-targeted therapies. However, recent discoveries which can also vital anti-tumour mechanisms cast doubt on this approach. review will explore myriad ways functions a regulator hallmarks cancer highlight role major microenvironment. The dual however, emphasises further investigation into defining precise mechanism action different settings.

Language: Английский

Citations

108