Role of ARK5 in cancer and other diseases (Review)

Mo, Guoheng; Zhang, Bohan; Jiang, Qunguang

doi:10.3892/etm.2021.10129

Cited by 11 publications

(9 citation statements)

References 137 publications

(234 reference statements)

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“…ARK5 is upregulated by MAF and MAFB through the MARE sequence in MM cells [ 58 ]. In several cancers, overexpression of ARK5 is related to tumor invasion, metastasis, and poor prognosis, with downregulation of ARK5 resulting in improved sensitivity to anti-tumor drugs [ 60 ]; thus, ARK5 is a potential therapeutic target in MM with t(14;16) or t(14;20).…”

Section: Pathogenic Role Of Cytogenetic Abnormalities In MMmentioning

confidence: 99%

Multiple myeloma with high-risk cytogenetics and its treatment approach

Hanamura

2022

Int J Hematol

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Despite substantial advances in anti-myeloma treatments, early recurrence and death remain an issue in certain subpopulations. Cytogenetic abnormalities (CAs) are the most widely accepted predictors for poor prognosis in multiple myeloma (MM), such as t(4;14), t(14;16), t(14;20), gain/amp(1q21), del(1p), and del(17p). Co-existing high-risk CAs (HRCAs) tend to be associated with an even worse prognosis. Achievement of sustained minimal residual disease (MRD)-negativity has recently emerged as a surrogate for longer survival, regardless of cytogenetic risk. Information from newer clinical trials suggests that extended intensified treatment can help achieve MRD-negativity in patients with HRCAs, which may lead to improved outcomes. Therapy should be considered to include a 3- or 4-drug induction regimen (PI/IMiD/Dex or PI/IMiD/Dex/anti-CD38 antibody), auto-transplantation, and consolidation/maintenance with lenalidomide ± a PI. Results from ongoing clinical trials for enriched high-risk populations will reveal the precise efficacy of the investigated regimens. Genetic abnormalities of MM cells are intrinsic critical factors determining tumor characteristics, which reflect the natural course and drug sensitivity of the disease. This paper reviews the clinicopathological features of genomic abnormalities related to adverse prognosis, focusing on HRCAs that are the most relevant in clinical practice, and outline current optimal therapeutic approaches for newly diagnosed MM with HRCAs.

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Section: Pathogenic Role Of Cytogenetic Abnormalities In MMmentioning

confidence: 99%

Multiple myeloma with high-risk cytogenetics and its treatment approach

Hanamura

2022

Int J Hematol

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“…Previous studies have shown that ARK5 is involved in the regulation of EMT processes in a variety of tumors [ 14 ]. Therefore, we speculate that ARK5 has a regulatory role in hepatocyte EMT during liver fibrosis.…”

Section: Resultsmentioning

confidence: 99%

“…ARK5 is a serine/threonine kinase and has been identified as an essential part of the catalytic subunit of the AMPK (AMP-activated protein kinase) family [ 14 ]. Previous studies have found that ARK5 participates in a number of significant functions such as cell adhesion, cell proliferation and metastasis, and carbohydrate metabolism [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…Aberrant expression of the ARK5 has been observed in a wide variety of solid tumors, including liver cancer, and positively correlates with the malignancy of cancer cells [ 16 , 17 , 18 ]. Recently, ARK5 has been identified as a gene that is strongly associated with fibrosis, TGF-β signaling, and poor outcomes in human chronic kidney disease [ 14 , 19 ]. However, the expression and TGF-β signaling interactions of the ARK5 during the development of liver fibrosis remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Enhanced Expression of ARK5 in Hepatic Stellate Cell and Hepatocyte Synergistically Promote Liver Fibrosis

You

Gao

et al. 2022

IJMS

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AMPK-related protein kinase 5 (ARK5) is involved in a broad spectrum of physiological and cell events, and aberrant expression of ARK5 has been observed in a wide variety of solid tumors, including liver cancer. However, the role of ARK5 in liver fibrosis remains largely unexplored. We found that ARK5 expression was elevated in mouse fibrotic livers, and showed a positive correlation with the progression of liver fibrosis. ARK5 was highly expressed not only in activated hepatic stellate cells (HSCs), but also in hepatocytes. In HSCs, ARK5 prevents the degradation of transforming growth factor β type I receptor (TβRI) and mothers against decapentaplegic homolog 4 (Smad4) proteins by inhibiting the expression of Smad ubiquitin regulatory factor 2 (Smurf2), thus maintaining the continuous transduction of the transforming growth factor β (TGF-β) signaling pathway, which is essential for cell activation, proliferation and survival. In hepatocytes, ARK5 induces the occurrence of epithelial-mesenchymal transition (EMT), and also promotes the secretion of inflammatory factors. Inflammatory factors, in turn, further enhance the activation of HSCs and deepen the degree of liver fibrosis. Notably, we demonstrated in a mouse model that targeting ARK5 with the selective inhibitor HTH-01-015 attenuates CCl4-induced liver fibrosis in mice. Taken together, the results indicate that ARK5 is a critical driver of liver fibrosis, and promotes liver fibrosis by synergy between HSCs and hepatocytes.

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“…Despite the limited number of studies that experimentally elucidate the role of NUAK1 and NUAK2 in cancer development, both kinases have been found amplified in different tumors. The role of NUAK1 in different tumor types has been recently reviewed in [38]. Here, we highlight the role of NUAK proteins in different pathways and their potential involvement in tumor initiation and propagation.…”

Section: Nuak1 and Nuak2 In Cancermentioning

confidence: 95%

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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Role of ARK5 in cancer and other diseases (Review)

Cited by 11 publications

References 137 publications

Multiple myeloma with high-risk cytogenetics and its treatment approach

Multiple myeloma with high-risk cytogenetics and its treatment approach

Enhanced Expression of ARK5 in Hepatic Stellate Cell and Hepatocyte Synergistically Promote Liver Fibrosis

NUAK Kinases: Brain–Ovary Axis

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