HUNK Signaling in Metastatic Breast Cancer

Dilday, Tinslee; ramos, N. K. Y.; Yeh, Elizabeth S.

doi:10.18632/oncoscience.504

Cited by 3 publications

(5 citation statements)

References 20 publications

(37 reference statements)

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“…Combined with GWAS results, 20 genes were simultaneously identified through GWAS and Fst analysis, out of them, SCAF4 , SOD1 , and TIAM1 were detected in two GWASs, and ENSSSCG00000048838 , ENSSSCG00000047227 , ENSSSCG00000043944 , ENSSSCG00000048577 , ENSSSCG00000042932 , ENSSSCG00000041405 , and ENSSSCG00000045589 were the novel genes. HUNK was involved in transferase activity, transfer phosphorus-containing groups, and protein tyrosine kinase activity, and was thought to play a role in breast cancer metastasis ( Dilday et al, 2020 ; Williams et al, 2020 ). ARHGDIB , RERG , and TMEM170B were also related to breast cancer ( Li et al, 2018 ; Huang et al, 2020 ; Wang et al, 2020 ), implying they might participate in the development of mammary glands.…”

Section: Discussionmentioning

confidence: 99%

Genetic parameters estimation and genome molecular marker identification for gestation length in pigs

Shi

Li²,

Wang³

2023

Front. Genet.

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Gestation length (GL) plays an important role in piglet maturation of major organs and development of body, while the genetic molecular markers of GL have not been extensively identified. In this study, according to the 5,662 effective records of 3,072 sows, the heritability and repeatability of GL were estimated through the dmuai of DMU Version 6.5.1 with a repeatability model, namely, h2 = 0.1594 and re2 = 0.2437. Among these sows, 906 individuals were genotyped with the GeneSeek Genomic Profiler (GGP) Porcine 50K Chip and imputed to the genome-wide level (9,212,179 SNPs) by the online software PHARP v1 for subsequent quality control and GWAS analyses. Further, the Fst was also performed to measure whether the actual frequency of genotypes in different GL phenotypes deviated from the theoretical proportion of genetic balance. We observed the highest degree of differentiation (average Fst value = 0.0376) in the group of 114 and 118 days, and identified a total of 1,002 SNPs strongly associated with GL. Through screening the genes located within a 500 kb distance on either side of the significant SNPs, we proposed 4,588 candidate genes. By the functional annotation, these candidates were found to be mainly involved in multicellular organism metabolism, early endosome, embryo implantation and development, and body and organ signaling pathway. Because of the simultaneous confirmation by GWAS and Fst analyses, there were 20 genes replied to be the most promising candidates including HUNK, ARHGDIB, ERP27, RERG, NEDD9, TMEM170B, SCAF4, SOD1, TIAM1, ENSSSCG00000048838, ENSSSCG00000047227, EDN1, HIVEP1, ENSSSCG00000043944, LRATD1, ENSSSCG00000048577, ENSSSCG00000042932, ENSSSCG00000041405, ENSSSCG00000045589, and ADTRP. This study provided effective molecular information for the genetic improvement of GL in pigs.

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Section: Discussionmentioning

confidence: 99%

Genetic parameters estimation and genome molecular marker identification for gestation length in pigs

Shi

Li²,

Wang³

2023

Front. Genet.

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“…HUNK is a serine/threonine kinase, and plays an important role in many cancer types, including CRC [ 7 , 24 ]. We speculated that HUNK exerts its biological functions through its kinase activity.…”

Section: Resultsmentioning

confidence: 99%

“…HUNK plays an important role in cancer cell proliferation, survival, as well as metastasis, and is an emerging therapeutic target for cancer treatments [ 7 , 8 , 10 , 28 – 32 ]. Clinically, we showed that HUNK protein levels are downregulated in metastatic CRC tissues in contrast to primary CRC tissues.…”

Section: Discussionmentioning

confidence: 99%

“…Hormonally Upregulated Neu-associated Kinase (HUNK), a serine-threonine protein kinase regulates cancer cell survival, proliferation and metastasis [ 7 ]. However, the controversial conclusions show that HUNK promotes or suppresses metastasis via various signaling pathways by either kinase-independent or -dependent way in breast cancer [ 8 – 10 ].…”

Section: Introductionmentioning

confidence: 99%

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HUNK inhibits epithelial-mesenchymal transition of CRC via direct phosphorylation of GEF-H1 and activating RhoA/LIMK-1/CFL-1

Han

Jiang

et al. 2023

Cell Death Dis

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Epithelial-mesenchymal transition (EMT) is associated with the invasive and metastatic phenotypes in colorectal cancer (CRC). However, the mechanisms underlying EMT in CRC are not completely understood. In this study, we find that HUNK inhibits EMT and metastasis of CRC cells via its substrate GEF-H1 in a kinase-dependent manner. Mechanistically, HUNK directly phosphorylates GEF-H1 at serine 645 (S645) site, which activates RhoA and consequently leads to a cascade of phosphorylation of LIMK-1/CFL-1, thereby stabilizing F-actin and inhibiting EMT. Clinically, the levels of both HUNK expression and phosphorylation S645 of GEH-H1 are not only downregulated in CRC tissues with metastasis compared with that without metastasis, but also positively correlated among these tissues. Our findings highlight the importance of HUNK kinase direct phosphorylation of GEF-H1 in regulation of EMT and metastasis of CRC.

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“…Hormonally upregulated neu-associated kinase (HUNK) is an approximately ~80 kDa serine/threonine (S/T) protein kinase that has been reported to be expressed in about 50% of breast carcinomas [ 1 , 2 , 3 , 4 ]. HUNK is part of the AMP-associated protein kinase (AMPK) family and plays a role in a variety of cellular processes, including the regulation of cell survival, proliferation, and autophagy [ 1 , 5 ]. While this protein was originally discovered in mouse mammary glands and is expressed in breast tissue, it has also been found in other organ systems such as the brain and central nervous system, and plays a role in diseases including colon cancer [ 3 , 4 , 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

HUNK Gene Alterations in Breast Cancer

et al. 2022

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Hormonally upregulated neu-associated kinase (HUNK) is a serine/threonine (S/T) protein kinase related to the adenosine monophosphate-activated protein kinase (AMPK) family of kinases. HUNK was originally discovered using a screen to identify kinases expressed in the mouse mammary gland. Therefore, the majority of studies to date have been carried out in models specific to this tissue, and the kinase was named to reflect its mammary gland-specific physiology and pathology. Prior studies show a clear pathogenic role for HUNK in breast cancer. HUNK is upregulated in response to oncogenic HER2/neu and Akt, and there is strong evidence that HUNK is critical for the survival of breast cancer cells. Further evidence shows that inhibiting HUNK using a variety of breast cancer models, including those that are resistant, inhibits tumorigenesis and metastasis. However, HUNK alterations are infrequent. Here, the incidence and consequence of HUNK alterations in breast cancer is reviewed using data mined from the online database cBioPortal and considered in relation to prior research studies.

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HUNK Signaling in Metastatic Breast Cancer

Cited by 3 publications

References 20 publications

Genetic parameters estimation and genome molecular marker identification for gestation length in pigs

Genetic parameters estimation and genome molecular marker identification for gestation length in pigs

HUNK inhibits epithelial-mesenchymal transition of CRC via direct phosphorylation of GEF-H1 and activating RhoA/LIMK-1/CFL-1

HUNK Gene Alterations in Breast Cancer

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