Deciphering the role of AMPK-related kinase 5 in human cancer progression and metastasis

Bambang, Alfredo; Tanadi, Caroline; Sumarpo, Anton

doi:10.15419/bmrat.v6i10.568

Cited by 3 publications

(4 citation statements)

References 46 publications

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“…Additionally, NUAK2 silencing has been associated with mTOR downregulation in cellular models of melanoma [48]. Therefore, NUAK proteins could possess tumor growth supporting functions given that the mTOR pathway is a pro-survival pathway commonly downregulated in cancer [49]. For instance, the pancreatic cancer cell line, PANC1, is very resistant to glucose starvation.…”

Section: Migration and Invasivenessmentioning

confidence: 99%

NUAK Kinases: Brain–Ovary Axis

Molina

Hong

Chefetz

2021

Cells

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Liver kinase B (LKB1) and adenosine monophosphate (AMP)-activated protein kinase (AMPK) are two major kinases that regulate cellular metabolism by acting as adenosine triphosphate (ATP) sensors. During starvation conditions, LKB1 and AMPK activate different downstream pathways to increase ATP production, while decreasing ATP consumption, which abrogates cellular proliferation and cell death. Initially, LKB1 was considered to be a tumor suppressor due to its loss of expression in various tumor types. Additional studies revealed amplifications in LKB1 and AMPK kinases in several cancers, suggesting a role in tumor progression. The AMPK-related proteins were described almost 20 years ago as a group of key kinases involved in the regulation of cellular metabolism. As LKB1-downstream targets, AMPK-related proteins were also initially considered to function as tumor suppressors. However, further research demonstrated that AMPK-related kinases play a major role not only in cellular physiology but also in tumor development. Furthermore, aside from their role as regulators of metabolism, additional functions have been described for these proteins, including roles in the cell cycle, cell migration, and cell death. In this review, we aim to highlight the major role of AMPK-related proteins beyond their functions in cellular metabolism, focusing on cancer progression based on their role in cell migration, invasion, and cell survival. Additionally, we describe two main AMPK-related kinases, Novel (nua) kinase family 1 (NUAK1) and 2 (NUAK2), which have been understudied, but play a major role in cellular physiology and tumor development.

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Section: Migration and Invasivenessmentioning

confidence: 99%

NUAK Kinases: Brain–Ovary Axis

Molina

Hong

Chefetz

2021

Cells

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“…However, upon development of carcinomatous cells, AMPK becomes an important driver for tumorigenesis [53]. In particular, AMPK related kinase 5 (ARK5) (also known as NUAK- 1) is a member of the AMPK class of serine/threonine protein kinases whose role as a cancer biomarker has been vastly studied [54]. ARK5 has been strongly associated with increased tumour invasiveness [55], tumour growth, metastasis [56], cellular survival in hypoxic and nutrient-deprived environments (austerity) [57], and epithelial mesenchymal transformation (EMT) in a wide range of human cancers [54,59].…”

Section: Ampk As a Driver Of Systemic Diseasementioning

confidence: 99%

“…In particular, AMPK related kinase 5 (ARK5) (also known as NUAK- 1) is a member of the AMPK class of serine/threonine protein kinases whose role as a cancer biomarker has been vastly studied [54]. ARK5 has been strongly associated with increased tumour invasiveness [55], tumour growth, metastasis [56], cellular survival in hypoxic and nutrient-deprived environments (austerity) [57], and epithelial mesenchymal transformation (EMT) in a wide range of human cancers [54,59]. Furthermore, there is evidence that ARK5 is involved in the pathogenesis of fibrosis and, importantly, that it is intrinsically linked with TGFß1 [60].…”

Section: Ampk As a Driver Of Systemic Diseasementioning

confidence: 99%

“…Several studies have highlighted promising therapeutic targets in halting or even reversing this progression, including nicotinamide, insulin and metformin. AMPK is a highly conserved master regulator of metabolism, both at the cellular and organismal levels, whose function is extremely relevant not only for normal physiology, but also for the understanding of many metabolic diseases [54]. The examination of novel mechanisms of AMPK as the key metabolic sensor in LC cells in glaucoma will be vital to understand the driving force underlying fibrotic changes occurring in the LC.…”

Section: Future Directions and Conclusionmentioning

confidence: 99%

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Untitled

2020

TOOAJ

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Glaucoma is the second leading cause of irreversible blindness worldwide. It is a multifactorial, progressive, chronic optic neuropathy that is characterized by loss of retinal ganglion cells (RGC) and optic nerve head (ONH) cupping including extra cellular matrix (ECM) remodelling and fibrosis at the lamina cribrosa (LC). Clinically this results in chronic, progressive peripheral visual field loss. The pathogenesis of glaucoma is not yet fully understood. Therefore, there is an urgent need to identify and target the underlying mechanisms governing ECM remodelling of the LC, in order to stop the progressive, chronic damage to the LC/ONH and irreversible visual field loss. This review identifies and examines some of the key metabolic processes and cellular sensors involved in the pathogenesis of ECM fibrosis in general but herein specifically in glaucoma, including mitochondrial dysfunction and adenosine monophosphate activated protein kinase (AMPK) upregulation. Furthermore, the development of novel therapeutics such as nicotinamide (NAM) and metformin are discussed as promising potential future therapeutic options for glaucoma.

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