Mesenchymal stem cells (MSCs) have been reported to localize in colorectal carcinomas, and participate in the formation of the tumor microenvironment. They have recently been isolated from colorectal cancer tissues, and are implicated in the growth, invasion, and metastasis of cancer cells. However, the roles and detailed mechanisms associated with human colorectal cancer-derived MSCs (CC-MSCs) have not been fully addressed. In this study, we found that CC-MSCs increased the migration and invasion of colorectal cancer cells and promoted the tumorigenesis of colorectal cancer through epithelial-to-mesenchymal transition (EMT) in vitro. We also found that CC-MSCs enhanced the growth and metastasis of colorectal cancer in vivo. Mechanistically, we determined that interleukin-6 (IL-6) was the most highly expressed cytokine in the CC-MSC conditioned medium, and promoted the progression of colorectal cancer cells through IL-6/JAK2/STAT3 signaling, which activated PI3K/AKT signaling. We used anti-IL-6 antibody to target IL-6. Collectively, these results reveal that the IL-6 secreted by CC-MSCs enhances the progression of colorectal cancer cells through IL-6/JAK2/STAT3 signaling, and could provide a novel therapeutic or preventive target.

Recent J-TEXT research has highlighted the significance of the role that non-axisymmetric magnetic perturbations, so called three-dimensional (3D) magnetic perturbation (MP) fields, play in a fundamentally 2D concept, i.e. tokamaks. This paper presents the J-TEXT results achieved over the last two years, especially on the impacts of 3D MP fields on magnetohydrodynamic instabilities, plasma disruptions and plasma turbulence transport. On J-TEXT, the resonant MP (RMP) system, capable of providing either a static or a high frequency (up to 8 kHz) rotating RMP field, has been upgraded by adding a new set of 12 in-vessel saddle coils. The shattered pellet injection system was built in J-TEXT in the spring of 2018. The new capabilities advance J-TEXT to be at the forefront of international magnetic fusion facilities, allowing flexible study of 3D effects and disruption mitigation in a tokamak. The fast rotating RMP field has been successfully applied for avoidance of mode locking and the prevention of plasma disruption. A new control strategy, which applies pulsed RMP to the tearing mode only during the accelerating phase region, was proved by nonlinear numerical modelling to be efficient in accelerating mode rotation and even completely suppresses the mode. Remarkably, the rotating tearing mode was completely suppressed by the electrode biasing. The impacts of 3D magnetic topology on the turbulence has been investigated on J-TEXT. It is found that the fluctuations of electron density, electron temperature and plasma potential can be significantly modulated by the island structure, and a larger fluctuation level appears at the X-point of islands. The suppression of runaway electrons during disruptions is essential to the operation of ITER, and it has been reached by utilizing the 3D magnetic perturbations on J-TEXT. This may provide an alternative mechanism of runaway suppression for large-scale tokamaks and ITER.

Extracellular cytokines are enriched in the tumor microenvironment and regulate various important properties of cancers, including autophagy. However, the precise molecular mechanisms underlying the link between autophagy and extracellular cytokines remain to be elucidated. In the present study, we demonstrate that IL-6 activates autophagy through the IL-6/JAK2/BECN1 pathway and promotes chemotherapy resistance in colorectal cancer (CRC). Mechanistically, IL-6 triggers the interaction between JAK2 and BECN1, where JAK2 phosphorylates BECN1 at Y333. We demonstrate that BECN1 Y333 phosphorylation is crucial for BECN1 activation and IL-6-induced autophagy by regulating PI3KC3 complex formation. Furthermore, we investigate BECN1 Y333 phosphorylation as a predictive marker for poor CRC prognosis and chemotherapy resistance. Combination treatment with autophagy inhibitors or pharmacological agents targeting the IL-6/JAK2/BECN1 signaling pathway may represent a potential strategy for CRC cancer therapy.