IndraLab

Statements

COPS6 binds FASN. 16 / 16
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"Wei et al [ xref ] reported that COP9 signalosome subunit 6 (CSN6) and the tumor suppressor F-box and WD repeat domain-containing 7 (FBXW7β) prevented the degradation of FASN; as a result, the CSN6-FASN axis eventually promoted lipogenesis and tumor growth."
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"Wei et al. found that CSN6 binds to both FBXW7β and FASN, and antagonizes the activity of FBXW7β by enhancing its self-ubiquitination and degradation, thereby preventing FBXW7β-mediated ubiquitination and degradation of FASN, actively regulating lipogenesis."
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"Furthermore, the EGF-regulated CSN6-FASN axis is a reason for poor prognosis in CRC."
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"Mechanistic studies show that CSN6 associates with both FBXW7β and FASN, and antagonizes FBXW7β’s activity by enhancing FBXW7β autoubiquitination and degradation, which in turn prevents FBXW7β-mediated FASN ubiquitination and degradation, thereby regulating lipogenesis positively."
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"Both CSN6 and FASN are positively correlated in CRC, and CSN6-FASN axis, regulated by EGF, is responsible for poor prognosis of CRC."
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"Thus, CSN6-FASN axis reprograms lipogenesis to promote tumor growth and is a target for cancer intervening strategy in CRC."
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"Co-immunoprecipitation (co-IP) assay revealed that CSN6 could bind to endogenous FASN in HCT 116 cells (Fig. 2b)."
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"To further support that CSN6 and FASN can form a complex in vivo, cellular proteins extracted from HCT-8 and HCT 116 cells were fractionated by gel-filtration chromatography for analysis."
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"The aberrant overexpression of CSN6-FASN axis in CRC leads to the metabolic reprogramming of lipid biosynthesis that instigates tumor growth and organoid formation, and results in poor cancer prognosis."
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"To further validate CSN6-FASN axis in terms of clinical significance, we analyzed the protein levels of FASN and CSN6 in CRC cell lines or tumor tissues."
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"To further explore whether controlling CSN6-FASN axis can mitigate the tumor development in CRC patients, we established patient-derived xenografts (PDXs) xref , xref by transplanting fresh primary CRC specimens into the NCG mice to analyze tumor growth (Fig. xref )."
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"CSN6 associates with lipogenesis regulator FASN and attenuates ubiquitin-mediated degradation of FASN to enhance FASN protein stability."
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"Co-immunoprecipitation (co-IP) assay revealed that CSN6 could bind to endogenous FASN in HCT 116 cells (Fig. xref )."
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"To further support that CSN6 and FASN can form a complex in vivo, cellular proteins extracted from HCT-8 and HCT 116 cells were fractionated by gel-filtration chromatography for analysis."
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"We characterized that CSN6 interacts with FASN through MPN domain in co-IP studies (Fig. xref )."
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"Further, fatty acid synthase can mediate EGFR palmitoylation, resulting in tyrosine kinase inhibitor (TKI) resistance in lung cancer. xref Our studies showed that CSN6-FASN axis increase palmitate production, implying that CSN6 may increase EGFR palmitoylation and possibly causes TKI-drug resistance."
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