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Che-1 sustains hypoxic response of colorectal cancer cells by affecting Hif-1α stabilization
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نویسنده
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bruno t. ,valerio m. ,casadei l. ,de nicola f. ,goeman f. ,pallocca m. ,catena v. ,iezzi s. ,sorino c. ,desantis a. ,manetti c. ,blandino g. ,floridi a. ,fanciulli m.
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منبع
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journal of experimental and clinical cancer research - 2017 - دوره : 36 - شماره : 1
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چکیده
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Background: solid tumours are less oxygenated than normal tissues. consequently,cancer cells acquire to be adapted to a hypoxic environment. the poor oxygenation of solid tumours is also a major indicator of an adverse cancer prognosis and leads to resistance to conventional anticancer treatments. we previously showed the involvement of che-1/aatf (che-1) in cancer cell survival under stress conditions. herein we hypothesized that che-1 plays a role in the response of cancer cells to hypoxia. methods: the human colon adenocarcinoma hct116 and ht29 cell lines undepleted or depleted for che-1 expression by sirna,were treated under normoxic and hypoxic conditions to perform studies regarding the role of this protein in metabolic adaptation and cell proliferation. che-1 expression was detected using western blot assays; cell metabolism was assessed by nmr spectroscopy and functional assays. additional molecular studies were performed by rna seq,qrt-pcr and chip analyses. results: here we report that che-1 expression is required for the adaptation of cells to hypoxia,playing an important role in metabolic modulation. indeed,che-1 depletion impacted on hif-1α stabilization,thus downregulating the expression of several genes involved in the response to hypoxia and affecting glucose metabolism. conclusions: we show that che-1 a novel player in the regulation of hif-1α in response to hypoxia. notably,we found that che-1 is required for siah-2 expression,a member of e3 ubiquitin ligase family that is involved in the degradation of the hydroxylase phd3,the master regulator of hif-1α stability. © 2017 the author(s).
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کلیدواژه
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Che-1/AATF; HIF-1α; Hypoxia; Metabolism; PHD3/EGLN3; SIAH-2
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آدرس
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uosd safu,department of research,diagnosis and innovative technologies,translational research area,regina elena national cancer institute,via e. chianesi 53,rome,00144, Italy, department of chemistry,sapienza university,rome, Italy, department of chemistry,sapienza university,rome, Italy, uosd safu,department of research,diagnosis and innovative technologies,translational research area,regina elena national cancer institute,via e. chianesi 53,rome,00144, Italy, uosd oncogenomic and epigenetic unit,regina elena national cancer institute,rome, Italy, uosd safu,department of research,diagnosis and innovative technologies,translational research area,regina elena national cancer institute,via e. chianesi 53,rome,00144, Italy, uosd safu,department of research,diagnosis and innovative technologies,translational research area,regina elena national cancer institute,via e. chianesi 53,rome,00144, Italy, uosd safu,department of research,diagnosis and innovative technologies,translational research area,regina elena national cancer institute,via e. chianesi 53,rome,00144, Italy, uosd safu,department of research,diagnosis and innovative technologies,translational research area,regina elena national cancer institute,via e. chianesi 53,rome,00144, Italy, uosd safu,department of research,diagnosis and innovative technologies,translational research area,regina elena national cancer institute,via e. chianesi 53,rome,00144, Italy, department of chemistry,sapienza university,rome, Italy, uosd oncogenomic and epigenetic unit,regina elena national cancer institute,rome, Italy, uosd safu,department of research,diagnosis and innovative technologies,translational research area,regina elena national cancer institute,via e. chianesi 53,rome,00144, Italy, uosd safu,department of research,diagnosis and innovative technologies,translational research area,regina elena national cancer institute,via e. chianesi 53,rome,00144, Italy
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