FBXW7βloss-of-function enhances FASN-mediated lipogenesis and promotes colorectal cancer growth

Continuous de novo fatty acid synthesis is required for the biosynthetic demands of tumor.FBXW7 is a highly mutated gene in CRC,but its biological functions in cancer are not fully characterized.Here,we report that FBXW7β,a FBXW7 isoform located in the cytoplasm and frequently mutated in CRC,is an E3 ligase of fatty acid synthase(FASN).Cancer-specific FBXW7βmutations that could not degrade FASN can lead to sustained lipogenesis in CRC.COP9 signalosome subunit 6(CSN6),an oncogenic marker of CRC,increases lipogenesis via interacting with and stabilizing FASN.Mechanistic studies show that CSN6 associates with both FBXW7βand FASN,and antagonizes FBXW7β’s activity by enhancing FBXW7βautoubiquitination and degradation,which in turn prevents FBXW7β-mediated FASN ubiquitination and degradation,thereby regulating lipogenesis positively.Both CSN6 and FASN are positively correlated in CRC,and CSN6-FASN axis,regulated by EGF,is responsible for poor prognosis of CRC.The EGF-CSN6-FASN axis promotes tumor growth and implies a treatment strategy of combination of orlistat and cetuximab.Patient-derived xenograft experiments prove the effectiveness of employing orlistat and cetuximab combination in suppressing tumor growth for CSN6/FASN-high CRC.Thus,CSN6-FASN axis reprograms lipogenesis to promote tumor growth and is a target for cancer intervening strategy in CRC.

Community structure and activity potentials of archaeal communities in hadal sediments of the Mariana and Mussau trenches

Hadal trenches are the least explored marine habitat on earth. Archaea has been shown to be the dominant group in trench sediments. However, the activity potentials and detailed diversity of these communities as well as their inter-trench variations are still not known. In this study, we combined datasets from two pairs of primers to investigate at high resolution the structure and activity potentials of the archaeal communities in vertically sectioned sediment cores taken from the deepest points of the Mariana (10,853 m) and Mussau (7011 m) trenches. The compositions of the potentially active communities revealed, via 16S ribosomal RNA gene (rDNA) and RNA (rRNA), significant differences between samples. Marine Group I (MGI), with nine identified subgroups, was the most dominant class in the active archaeal communities of the two trenches. Significantly different species composition and vertical variations were observed between the two trenches. Vertical transitions from aerobic MGI α to anaerobic MGI η and υ subgroups were observed in MST but not in MT sediments, which might be related to the faster microbial oxygen consumption in MST. These results provide a better understanding on archaeal activity and diversity in trench sediments.