Akt kinase plays a central role in cell growth, metabolism and tumorigenesis. Although TRAF6 E3 ligase orchestrates IGF-1-mediated Akt ubiquitination and activation, it is unclear whether TRAF6 is involved in Akt activation by other growth factor receptors as well. Here we show that Akt ubiquitination is also induced by activation of ErbB receptors; unexpectedly, Skp2 SCF complex, but not TRAF6, is a critical E3 ligase for ErbB receptor-mediated Akt ubiquitination and membrane recruitment. Interestingly, Skp2 deficiency impairs Akt activation, Glut1 expression, glucose uptake and glycolysis, and breast cancer progression in various tumor models. Moreover, Skp2 overexpression correlates with Akt activation, breast cancer metastasis, and serves as a marker for poor prognosis in Her2-positive patients. Finally, we showed that Skp2 silencing sensitizes Her2-overexpressing tumors to Herceptin treatment. Our study suggests that distinct E3 ligases are utilized by diverse growth factors for Akt ubiquitination and activation.
We have developed a prototype PET detector which is compatible with a clinical MRI system to provide simultaneous PET and MR imaging. This single-slice PET system consists of 48 2 x 2 x 10 mm3 LSO crystals in a 38 mm diameter ring configuration that can be placed inside the receiver coil of the MRI system, coupled to three multi-channel photomultipliers housed outside the main magnetic field via 4 m long and 2 mm diameter optical fibres. The PET system exhibits 2 mm spatial resolution, 41% energy resolution at 511 keV and 20 ns timing resolution. Simultaneous PET and MR phantom images were successfully acquired.
The above article reported an important role of Skp2 in Akt activation, glycolysis, and Herceptin sensitivity. During the course of preparing Figure 6F, we inadvertently redisplayed the image from the HE (4003) image for Metastatic (M), Neu/Skp2 À/À column (fourth image on the bottom row) as the HE ( 4003) image for Metastatic (M), Neu column (third image on the bottom row). The corrected figure, which does not affect the results and interpretation as discussed in the paper, appears below and with the article online. We sincerely regret our error and apologize for the inconvenience that it may have caused.
We report the development of a prototype positron emission tomography (PET) scanner compatible with clinical magnetic resonance imaging (MRI) scanners and nuclear magnetic resonance (NMR) spectrometers. This single slice PET system consists of 72 2 x 2~5 mm lutetium oxyorthosilicate (LSO) crystals coupled by 2 mm diameter, 4 meter long double clad optical fibers to three multi-channel photomultiplier tubes (MC-PMT's) shielded inside an aluminum closure. The ring diameter is 54 mm and the slice thickness is -1 mm FWHM. Measurements with a point source demonstrate that this PET system has a reconstructed resolution of 2.1 mm, a coincidence time resolution of 26 ns and a typical energy resolution of 45%. Simultaneously acquired PET and MR phantom images show no significant artifacts or distortions. We also obtained simultaneous NMR spectra and PET images from an isolated, perfused rat heart, demonstrating the power of obtaining temporally correlated PET and NMR information in biological systems. Again, no artifacts in the PET or NMR data were apparent, despite the high field strength of 9.4T. The challenge for the future is to scale up the design to develop a high resolution, high sensitivity device that can be used in simultaneous PET and MR studies of in vivo systems.
Summary
Extensive reprogramming of cellular energy metabolism is a hallmark of cancer. Despite its importance, the molecular mechanism controlling this tumour metabolic shift remains not fully understood. Here we show that 14-3-3σ regulates cancer metabolic reprogramming and protects cells from tumourigenic transformation. 14-3-3σ opposes tumour-promoting metabolic programs by enhancing c-Myc poly-ubiquitination and subsequent degradation. 14-3-3σ demonstrates the suppressive impact on cancer glycolysis, glutaminolysis, mitochondrial biogenesis and other major metabolic processes of tumours. Importantly, 14-3-3σ expression levels predict overall and recurrence-free survival rates, tumour glucose uptake and metabolic gene expression in breast cancer patients. Thus, these results highlight that 14-3-3σ is an important regulator of tumour metabolism, and loss of 14-3-3σ expression is critical for cancer metabolic reprogramming. We anticipate that pharmacologically elevating the function of 14-3-3σ in tumours could be a promising direction for targeted anti-cancer metabolism therapy development in future.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.