The regulation and function of the NUAK family

Sun, Xianglan; Gao, Ling; Chien, Hung Yu; Li, Wan Chun; Zhao, Jiajun

doi:10.1530/jme-13-0063

Cited by 62 publications

(58 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AMPK, at present, is already known to act as a tumor suppressor through interacting with a network of complex structures in cancer cells. ARK5, one of members of AMPK family, is considered as be involved in cancer invasion and metastasis as a result of its great sequence homology to the catalytic domain of AMPK [25]. ARK5 was first deemed as a tumor malignancy-associated factor in Akt-induced cell migration activity in human pancreatic and colon cancer cells [13].…”

Section: Discussionmentioning

confidence: 99%

Knockdown of ARK5 Expression Suppresses Invasion and Metastasis of Gastric Cancer

Chen¹,

Liu²,

Xu³

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Gastric cancer (GC) is a common and lethal malignancy, and AMP-activated protein kinase-related kinase 5 (ARK5) has been discovered to promote cancer metastasis in certain types of cancer. In this study, we explored the role of ARK5 in GC invasion and metastasis. Methods: ARK5 and epithelial-mesenchymal transition (EMT)-related markers were determined by immunohistochemistry and western blot in GC specimens. Other methods including stably transfected against ARK5 into SGC7901 and AGS cells, western blot, migration and invasion assays in vitro and nude mice tumorigenicity in vivo were also employed. Results: The results demonstrated that ARK5 expression was increased and positively correlated with metastasis, EMT-related markers and poor prognosis in patients with GC. Knockdown of ARK5 expression remarkably suppressed GC cells invasion and metastasis via regulating EMT, rather than proliferation in vitro and in vivo. And knockdown of ARK5 expression in GC cells resulted in the down-regulation of the mTOR/p70S6k signals, Slug and SIP1. Conclusion: The elevated ARK5 expression was closely associated with cancer metastasis and patient survival, and it seemed to function in GC cells migration and invasion via EMT alteration, together with the alteration of the mTOR/p70S6k signals, Slug and SIP1, thus providing a potential therapeutic target for GC.

show abstract

Section: Discussionmentioning

confidence: 99%

Knockdown of ARK5 Expression Suppresses Invasion and Metastasis of Gastric Cancer

Chen¹,

Liu²,

Xu³

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…ULK1 is a substrate of AMPK and a key regulator of autophagy (50) and was recently reported to promote the growth of HER2 þ breast cancer cells (51). NUAK2 is an AMPK-related kinase and a putative oncogene in melanoma (52,53). RIOK2 regulates glioblastoma growth and survival via regulating AKT (54).…”

Section: Discussionmentioning

confidence: 99%

CLK2 Is an Oncogenic Kinase and Splicing Regulator in Breast Cancer

et al. 2015

View full text Add to dashboard Cite

Genetically activated kinases have been attractive therapeutic targets in cancer due to the relative ease of developing tumorspecific treatment strategies for them. To discover novel putative oncogenic kinases, we identified 26 genes commonly amplified and overexpressed in breast cancer and subjected them to a lentiviral shRNA cell viability screen in a panel of breast cancer cell lines. Here, we report that CLK2, a kinase that phosphorylates SR proteins involved in splicing, acts as an oncogene in breast cancer. Deregulated alternative splicing patterns are commonly observed in human cancers but the underlying mechanisms and functional relevance are still largely unknown. CLK2 is amplified and overexpressed in a significant fraction of breast tumors. Downregulation of CLK2 inhibits breast cancer growth in cell culture and in xenograft models and it enhances cell migration and invasion. Loss of CLK2 in luminal breast cancer cells leads to the upregulation of epithelial-to-mesenchymal transition (EMT)-related genes and a switch to mesenchymal splice variants of several genes, including ENAH (MENA). These results imply that therapeutic targeting of CLK2 may be used to modulate EMT splicing patterns and to inhibit breast tumor growth. Cancer Res; 75(7); 1516-26.Ó2015 AACR.

show abstract

“…Of these, AMPK itself has been investigated extensively and is established as an important regulator of skeletal muscle metabolism and adaptation in response to stress (9,10), whereas very little is known about the function of other AMPK-related kinases in muscle. The SNF1-AMPK-related kinase, SNARK (also known as NUAK2), has been implicated in the regulation of critical cellular processes, including metabolism (11) and cell motility (12), and its expression is regulated by disease states in humans, such as cancer (13) and obesity (14). Homozygous deletion of SNARK in mice is lethal at an embryonic stage, suggesting an essential role for SNARK in development (15).…”

Section: Introductionmentioning

confidence: 99%