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| Status |
Public on Jun 12, 2017 |
| Title |
Che-1 sustains hypoxic response of colorectal cancer cells by affecting Hif-1α stabilization |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Solid tumors are less oxygenated than normal tissues, and for this reason the cancer cells have developed several molecular mechanisms of adaptation to hypoxic environment. Moreover, his poor oxygenation is a major indicator of an adverse prognosis and leads resistance to standard anticancer treatment. Previous reports from this laboratory showed an involvement of Che-1/AATF (Che-1) in cancer cell survival under stress conditions, and on the basis of these observations, we hypothesized that Che-1 might have a role in the response of cancer cells to hypoxia.
Methods: The human colon adenocarcinoma cell line HCT116 depleted or not for Che-1 by siRNA, was subjected to normoxic and hypoxic conditions to perform studies about the role of this protein in metabolic adaptation and cell proliferation. The expression of Che-1 under normoxia or hypoxia was detected using western blot assays; cell metabolism was assessed by NMR spectroscopy and functional assays. Further molecular studies were performed by RNA seq, qRT-PCR and ChIP analysis.
Results: In this paper we report that Che-1 expression is required for the adaptation of the cells to hypoxia, playing and important role in metabolic modulation. Indeed, Che-1 depletion impacted on glycolysis by altering the expression of several genes involved in the response to hypoxia by modulating the levels of HIF-1alpha.
Conclusions: These data demonstrate a novel player in the regulation of a HIF1alpha in response to hypoxia. We found that the transcriptional down-regulation of a members of E3 ubiquitin ligase family SIAH2 by Che-1, produces a failure in the degradation by the hydroxylase PHD3 with a decrease in HIF-1alpha levels during hypoxia.
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| Overall design |
The human colon adenocarcinoma cell line HCT116 depleted or not for Che-1 by siRNA was profiled for mRNA high-troughput sequencing (RNA-seq)
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| Contributor(s) |
Tiziana B, Matteo P, Maurizio F |
| Citation(s) |
28214471 |
| Submission date |
Nov 28, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Matteo Pallocca |
| Organization name |
Italian National Cancer Institute "Regina Elena"
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| Street address |
Via Fermo Ognibene
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| City |
Rome |
| ZIP/Postal code |
00144 |
| Country |
Italy |
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| Platforms (1) |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA356445 |
| SRA |
SRP094652 |
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