HSL119 results in gene expression changes equivalent to HUNK shRNA
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE233608 | GEO | 2023/12/05
REPOSITORIES: GEO
Similar Datasets
Project description:HSL119 results in gene expression changes equivalent to HUNK shRNA
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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: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: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: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:Hunk as aregulator of TNBC genes involve in tumor immunity
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Project description:Faratian2009 - Role of PTEN in Trastuzumab
resistance
This model is described in the article:
Systems biology
reveals new strategies for personalizing cancer medicine and
confirms the role of PTEN in resistance to trastuzumab.
Faratian D, Goltsov A, Lebedeva G,
Sorokin A, Moodie S, Mullen P, Kay C, Um IH, Langdon S, Goryanin
I, Harrison DJ.
Cancer Res. 2009 Aug; 69(16):
6713-6720
Abstract:
Resistance to targeted cancer therapies such as trastuzumab
is a frequent clinical problem not solely because of
insufficient expression of HER2 receptor but also because of
the overriding activation states of cell signaling pathways.
Systems biology approaches lend themselves to rapid in silico
testing of factors, which may confer resistance to targeted
therapies. Inthis study, we aimed to develop a new kinetic
model that could be interrogated to predict resistance to
receptor tyrosine kinase (RTK) inhibitor therapies and directly
test predictions in vitro and in clinical samples. The new
mathematical model included RTK inhibitor antibody binding,
HER2/HER3 dimerization and inhibition, AKT/mitogen-activated
protein kinase cross-talk, and the regulatory properties of
PTEN. The model was parameterized using quantitative
phosphoprotein expression data from cancer cell lines using
reverse-phase protein microarrays. Quantitative PTEN protein
expression was found to be the key determinant of resistance to
anti-HER2 therapy in silico, which was predictive of unseen
experiments in vitro using the PTEN inhibitor bp(V). When
measured in cancer cell lines, PTEN expression predicts
sensitivity to anti-HER2 therapy; furthermore, this
quantitative measurement is more predictive of response
(relative risk, 3.0; 95% confidence interval, 1.6-5.5; P <
0.0001) than other pathway components taken in isolation and
when tested by multivariate analysis in a cohort of 122 breast
cancers treated with trastuzumab. For the first time, a systems
biology approach has successfully been used to stratify
patients for personalized therapy in cancer and is further
compelling evidence that PTEN, appropriately measured in the
clinical setting, refines clinical decision making in patients
treated with anti-HER2 therapies.
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2024-09-02 | BIOMD0000000424 | BioModels
Project description:The AKT inhibitor MK2206 (M) was one of the experimental agents evaluated in I-SPY 2, a neoadjuvant platform trial for high risk, early stage breast cancer, and graduated in the HER2+, HR-, and HR-HER2+ signatures. Based on the hypotheses that since MK2206 is an enzymatic inhibitor of AKT, response to MK2206 may be predicted by the relative pre-treatment levels of AKT kinase substrates, in pre-defined analyses we assessed 10 genes in the HER-AKT-mTOR pathway to test their association with pCR (complete pathologic response) in the MK2206 arm, in both HER2+ and HER2- subsets. We also tested 9 genes genes previously associated with response to MK2206 in vitro and in the HER2+ metastatic setting, and performed exploratory association analyses using whole-transcriptome data to identify additional predictive signals outside the HER-AKT-mTOR pathway.
2020-09-20 | GSE149322 | GEO
Project description:Hypoxia inhibits HUNK-mediated phosphorylation of GEF-H1 for epithelial-to-mesenchymal transition
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