Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-14226
PROVIDER: PRJNA111263 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We previously identified a novel SNF1/AMPK-related protein kinase, Hunk, from a mammary tumor arising in an MMTV-neu transgenic mouse. The function of this kinase is unknown. Using targeted deletion in mice, we now demonstrate that Hunk is required for the metastasis of c-myc-induced mammary tumors, but is dispensable for normal development. Reconstitution experiments revealed that Hunk is sufficient to restore the metastatic potential of Hunk-deficient tumor cells, as well as defects in migration and invasion, and does so in a manner that requires its kinase activity. Consistent with a role for Hunk in the progression of human cancers, the human homologue of Hunk is overexpressed in aggressive subsets of carcinomas of the ovary, colon, and breast. In addition, a murine gene expression signature that distinguishes Hunk-wild type from Hunk-deficient mammary tumors predicts clinical outcome in women with breast cancer. Together, these findings establish a role for Hunk in metastasis and an in vivo function for this kinase.
2009-12-31 | GSE14226 | GEO
Project description:We previously identified a novel SNF1/AMPK-related protein kinase, Hunk, from a mammary tumor arising in an MMTV-neu transgenic mouse. The function of this kinase is unknown. Using targeted deletion in mice, we now demonstrate that Hunk is required for the metastasis of c-myc-induced mammary tumors, but is dispensable for normal development. Reconstitution experiments revealed that Hunk is sufficient to restore the metastatic potential of Hunk-deficient tumor cells, as well as defects in migration and invasion, and does so in a manner that requires its kinase activity. Consistent with a role for Hunk in the progression of human cancers, the human homologue of Hunk is overexpressed in aggressive subsets of carcinomas of the ovary, colon, and breast. In addition, a murine gene expression signature that distinguishes Hunk-wild type from Hunk-deficient mammary tumors predicts clinical outcome in women with breast cancer. Together, these findings establish a role for Hunk in metastasis and an in vivo function for this kinase. Hunk-deficient animals were crossed to mice harboring an MMTV-c-myc transgene (Leder et al., 1986). Hunk heterozygous, MMTV-c-myc mice were backcrossed to Hunk heterozygous animals. MMTV-c-myc female animals of each Hunk genotype were mated twice, then monitored twice weekly for mammary tumors. Mice possessing tumors with a maximum diameter of 20 mm were sacrificed and organs were examined at necropsy. Tumor nodules were identified by examination of organs through a Leica Wild MZ8 dissection microscope.
2009-12-31 | E-GEOD-14226 | biostudies-arrayexpress
Project description:Hypoxia regulates epithelial to mesenchymal transition (EMT) of cancer cells. However, the mechanism underlying hypoxia-mediated EMT remains largely unknow. Here, utilizing colorectal cell carcinoma (CRC) as a model, we find that HUNK inhibits EMT and suppresses metastasis of CRC cells via its substrate GEF-H1 in a kinase-dependent manner. Mechanistically, HUNK directly phosphorylates GEF-H1 at ser645 site, which activates RhoA and consequently leads to a cascade of phosphorylation of LIMK1/CFL-1, thereby stabilizing F-actin and inhibiting EMT. Moreover, hypoxia suppresses HUNK activity and dephosphorylates GEF-H1 to promote EMT. Clinically, the expression levels of both HUNK and phosphorylation of GEH-H1 ser645 are not only downregulated in CRC tissues with metastasis compared to that without metastasis, but also positively correlated among these tissues. Our findings highlight the importance of hypoxia-regulated HUNK kinase activity and phosphorylation of GEF-H1 in regulation of EMT and metastasis of CRC.
2022-05-27 | GSE203440 | GEO
Project description:Metastasis constitutes a hallmark of cancer and serves as the principal cause of cancer-related mortality. Nevertheless, the mechanism of liver metastasis in CRC remains incompletely clarified. This study investigates the long non-coding RNA (lncRNA) SLERT and its critical role in promoting liver metastasis of colorectal cancer (CRC) by downregulating HUNK expression. We found that SLERT was significantly upregulated in CRC tissues, correlating with poorer survival outcomes. Functional assays revealed that silencing SLERT inhibited CRC cell migration and invasion, while its overexpression promoted these metastatic behaviors. Mechanistic analysis showed that SLERT interacts with the RNA-binding protein RBM15, impairing its ability to stabilize HUNK mRNA, leading to decreased HUNK levels and increased metastatic potential. The cytoplasmic localization of SLERT indicates its active role in regulating gene expression within the tumor microenvironment. Collectively, these results suggest that SLERT serves as a potential diagnostic biomarker and therapeutic target, indicating that targeting SLERT or restoring HUNK expression could provide novel strategies to combat liver metastasis in CRC and improve patient prognosis.
2025-01-01 | GSE284657 | GEO
Project description: Not available
| S-EPMC8784167 | biostudies-literature
Project description:The goal of this study was to target tumor immune specific genes and allowed us to specifically immune profiling what genes are change in HUNK or HUNK knockdown groups. A main objective was to determine if genes related to the citokine signaling pathway were changed in HUNK control compared to HUNK knockdown groups.
2024-06-12 | GSE242859 | GEO
Project description:Janus kinase 1 is essential for inflammatory cytokine signaling and mammary gland remodeling
| PRJNA315865 | ENA
Project description:Transcription profiling by array of mammary gland tissues from Hunk (a novel SNF1/AMPK-related protein kinase) knockout and wild type controls
2014-07-09 | E-GEOD-14226 | ExpressionAtlas
Project description:Comparison of matched primary and metastasis 4T1.2 syngeneic mammary tumor model of spontaneous bone metastasis
| PRJNA165849 | ENA
Project description: Not available
| S-EPMC11335981 | biostudies-literature