Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
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Target Concepts:
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Query: UMLS:C0699790 (
colon cancer
)
28,837
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Natural products are interesting sources for drug discovery. The natural product oxadiazine Nocuolin A (NocA) was previously isolated from the cyanobacterial strain
Nodularia
sp. LEGE 06071 and here we examined its cytotoxic effects against different strains of the
colon cancer
cell line HCT116 and the immortalized epithelial cell line hTERT RPE-1. NocA was cytotoxic against
colon cancer
cells and immortalized cells under conditions of exponential growth but was only weakly active against non-proliferating immortalized cells. NocA induced apoptosis by mechanism(s) resistant to overexpression of BCL family members. Interestingly, NocA affected viability and induced apoptosis of HCT116 cells grown as multicellular spheroids. Analysis of transcriptome profiles did not match signatures to any known compounds in CMap but indicated stress responses and induction of cell
starvation
. Evidence for autophagy was observed, and a decrease in various mitochondrial respiration parameter within 1 h of treatment. These results are consistent with previous findings showing that nutritionally compromised cells in spheroids are sensitive to impairment of mitochondrial energy production due to limited metabolic plasticity. We conclude that the antiproliferative effects of NocA are associated with effects on mitochondrial oxidative phosphorylation.
...
PMID:Antiproliferative Effects of the Natural Oxadiazine Nocuolin A Are Associated With Impairment of Mitochondrial Oxidative Phosphorylation. 3100 82
Alternative pre-mRNA-splicing-induced post-transcriptional gene expression regulation is one of the pathways for tumors maintaining proliferation rates accompanying the malignant phenotype under stress. Here, we uncover a list of hyperacetylated proteins in the context of acutely reduced Acetyl-CoA levels under nutrient
starvation
. PHF5A, a component of U2 snRNPs, can be acetylated at lysine 29 in response to multiple cellular stresses, which is dependent on p300. PHF5A acetylation strengthens the interaction among U2 snRNPs and affects global pre-mRNA splicing pattern and extensive gene expression. PHF5A hyperacetylation-induced alternative splicing stabilizes KDM3A mRNA and promotes its protein expression. Pathologically, PHF5A K29 hyperacetylation and KDM3A upregulation axis are correlated with poor prognosis of
colon cancer
. Our findings uncover a mechanism of an anti-stress pathway through which acetylation on PHF5A promotes the cancer cells' capacity for stress resistance and consequently contributes to colon carcinogenesis.
...
PMID:Acetylation of PHF5A Modulates Stress Responses and Colorectal Carcinogenesis through Alternative Splicing-Mediated Upregulation of KDM3A. 3105 74
Epigenetic alterations, especially histone modification, play vital roles in the pathogenesis of
colon cancer
. Upregulation of the enhancer of zeste homolog 2 (EZH2) has been reported to contribute to the initiation and progression of
colon cancer
. This study analyzed the association between EZH2 and phosphorylation of H2B at tyrosine 37 (H2B
Y37ph
) in
colon cancer
tissues and cells, along with the influences of the EZH2-H2B
Y37ph
axis on
colon cancer
cell autophagy. Immunohistochemistry was utilized to assess EZH2 and H2B
Y37ph
expressions in clinical samples of
colon cancer
. Cell transfection was carried out to alter EZH2 and H2B
Y37ph
expressions in
colon cancer
cells. Co-immunoprecipitation analysis and glutathione-S-transferase (GST) pull down assay were conducted to analyze the association between EZH2 and H2B
Y37ph
. Western blotting was utilized to measure proteins expressions related to cell autophagy. We found that there was a positive association between EZH2 and H2B
Y37ph
in
colon cancer
tissues and cells. EZH2 directly interacted with H2B and promoted H2B
Y37ph
in
colon cancer
cells using ATP as a phosphate donor. Moreover, EZH2 levated
colon cancer
cell autophagy in
starvation
condition. H2B
Y37ph
was required for EZH2-elevated
colon cancer
cell autophagy under
starvation
condition. The EZH2-H2B
Y37ph
axis elevated
colon cancer
cell autophagy possibly via activating transcriptional regulation of ATG genes. In conclusion, EZH2-elevated
colon cancer
initiation and progression at least in part via inducing
colon cancer
cell autophagy. EZH2 could phosphorylate H2B
Y37
and then induce transcription activation of ATG genes in
colon cancer
cells under
starvation
condition.
...
PMID:EZH2 regulates H2B phosphorylation and elevates colon cancer cell autophagy. 3128 6
Objective:
To investigate Livin-mediated regulation of H2A.X
Y142
phosphorylation via a novel kinase activity and its effect on autophagy in
colon cancer
cells.
Methods:
The interaction between Livin and H2A.X was tested by immunoprecipitation. H2A.X-/- HCT116 cells were transfected with human influenza hemagglutinin (HA)-tagged WT or Y142F phospho-dead mutantH2A.X plasmids. GST-tagged recombinant Livin protein was used to perform
in vitro
pull-down experiment and kinase assay. H2A.X-/-Livin+/+ SW480 cells were co-transfected with H2A.X
WT
/H2A.X
Y142F
plasmid and LC3 EGFP-tagged plasmid to explore whether H2A.X
Y142F
was involved in Livin-mediated autophagy induced by
starvation
in
colon cancer
cells.
Results:
Co-immunoprecipitation studies confirmed that Livin interacted with H2A.X and that it was phosphorylation dependent.
In vitro
kinase assay confirmed that Livin could phosphorylate H2A.X. Knockdown of Livin (Livin-/-) in SW480 cells or HCT116 cells canceled the
starvation
-induced autophagy in
colon cancer
cells; H2A.X-/-Livin+/+ SW480 cells transfected with H2A.X
WT
activated autophagy induced by
starvation
while cells transfected with H2A.X
Y142F
had no significant difference; Livin-H2A.X
Y142F
axis activated autophagy in
colon cancer
cells through transcriptionally regulating
ATG5
and
ATG7
.
Conclusion:
Livin promotes autophagy in
colon cancer
cells via regulating the phosphorylation of H2A.X
Y142
.
...
PMID:Livin Regulates H2A.X
Y142
Phosphorylation and Promotes Autophagy in Colon Cancer Cells via a Novel Kinase Activity. 3179 93
Modulation of fatty acids metabolism is an appropriate strategy for
starvation
-induced death in tumor cancers.
Colon cancer
cells express a high level of acyl-CoA synthetase-5 (ACSL5), and as yet no therapeutic approach has been achieved. Herein, ACSL5-related microRNAs (miRNAs) were identified via TargetScan, and their impacts on ACSL5 and lipid content along with metabolic activity, cell cycle, migration, and invasion of colorectal cancer (CRC) cells were examined, and subsequently compared with transcriptome for better visualization of intracellular-signaling networks. In vivo analysis was performed using BALB/c mice xenograft model of CRC injected with target miRNA. Clinical significances were also evaluated in 80 CRC tumors and matched adjacent normal tissues. There was a reverse correlation between ACSL5 and miR-497-5p, which miR-497-5p overexpression modulated CRC cell proliferation and development. A similar observation was received from the in vivo examination in which intratumoral injection of miR-497-5p reversed the tumor growth in the CRC xenograft model. Downregulation of miR-497-5p correlated with tumor differentiation, tumor, node, and metastasis staging, lymph node metastasis, and poor survival in patients with CRC. These results suggested that miR-497-5p upregulation could be considered as a therapeutic strategy for modulation of lipid metabolism in
colon cancer
.
...
PMID:miR-497-5p mediates starvation-induced death in colon cancer cells by targeting acyl-CoA synthetase-5 and modulation of lipid metabolism. 3201 65
Cancer stem cells (CSCs) are a small and elusive subpopulation of self-renewing cancer cells with remarkable ability to initiate, propagate, and spread the malignant disease. In addition, they exhibit increased resistance to anticancer therapies, thereby contributing to disease relapse. CSCs are reported to be present in many tumor types such as melanoma, sarcoma, mammary tumors,
colon cancer
and other solid tumors. These cells from different tumors show unique energetic and metabolic pathways. For example, CSCs from one type of tumor may predominantly use aerobic glycolysis, while from another tumor type may utilize oxidative phosphorylation. Most commonly these cells use fatty acid oxidation and ketone bodies as the main source of energy production. CSCs have a remarkable ability to reprogram their metabolism in order to survive under adverse conditions such as hypoxia, acidosis, and
starvation
. There is increasing interest to identify molecular targets that can be utilized to kill CSCs and to control their growth. In this review, we discuss how an understanding of the unique metabolism of CSCs from different tumors can offer promising strategies for targeting CSCs and hence to prevent disease relapse and to treat the metastatic disease.
...
PMID:Metabolic Adaptations in Cancer Stem Cells. 3267 Aug 83
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