Vps34, a class III PtdIns3 lipid kinase involved in the control of both autophagic and endocytic systems, has been studied extensively in numerous fundamental cellular processes. Accumulating evidence indicates that Vps34 may also contribute to the development and progression of human cancers. However, the mechanism of Vps34 in tumorigenesis remains elusive. Here, we report an unanticipated role of Vps34 in the activation of p62 for cancer development. We identified that Vps34 is a transcriptional activator of p62 through competition of Nrf2 (nuclear factor erythroid 2-related factor 2) for Keap1 binding. Vps34 augments the association of PKC-δ with p62 for its phosphorylation at Serine 349, which leads to positive feedback on the Nrf2-dependent transcription of oncogenes. Additionally, we found that the expression of Vps34 is correlated with the tumorigenic activity of human breast cancer cells. Normally inactive in breast cancer, caspase 8 can cleave Vps34 at residue D285, which directly abolished its lipid kinase activity and dramatically altered cell invasion potential, colony formation, as well as tumorigenesis in orthotopic engraftments in mice. The cleavage at D285 blocks expression of LC3-II, Nrf2 and subsequently, p62, in addition to blocking tumor growth, indicating that the intact structure of Vps34 is essential for its activity. Moreover, either knockout of PKC-δ or knockdown of p62 by small interfering RNA in MCF-7 cells abrogates Vps34-dependent tumor growth. Data presented here suggested that Vps34 stimulates tumor development mainly through PKC-δ- activation of p62.

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We investigate the electrical detection of anisotropic antiferromagnetic/ferromagnetic (AFM/FM) domain walls in (2 at%) Pd-doped FeRh films. The Hall signals keep almost at zero at both AFM and FM states, while a sizeable Hall conductivity up to 300 (Ω cm)−1 emerges during the AFM–FM phase transition of Pd-doped FeRh films around room temperature. Such Hall signals could be ascribed to the transverse current scattered by the anisotropic AFM/FM domain walls, which are mainly aligned around the [1 0 0] axis of the Pd-doped FeRh films. The highly reproducible Hall signals in both the temperature and magnetic field-induced magnetic phase transition are supported by the observation of a nonrandom formation of AFM/FM domain walls. Our findings not only advance the understanding of the magnetic phase transitions, but also propose a considerable way for the detection of AFM/FM domain walls by an electrical means.