TREM2 (triggering receptor expressed on myeloid cells) is involved in the development of malignancies. However, the function of TREM2 in colorectal cancer has not been clearly elucidated. Here, we investigated TREM2 function for the first time in colorectal epithelial cancer cells and demonstrated that TREM2 is a novel tumor suppressor in colorectal carcinoma. Blockade of TREM2 significantly promoted the proliferation of HT29 colorectal carcinoma cells by regulating cell cycle-related factors, such as p53 phosphorylation and p21 and cyclin D1 protein levels. HT29 cell migration was also increased by TREM2 inhibition via MMP9 (matrix metalloproteinase 9) expression upregulation. Furthermore, we found that the tumor suppressor effects of TREM2 were associated with Wnt/β-catenin and extracellular signal-regulated kinase (ERK) signaling. Importantly, the effect of TREM2 in the suppression of tumor development was demonstrated by in vivo and in vitro assays, as well as in human colon cancer patient tissue arrays. Overall, our results identify TREM2 as a potential prognostic biomarker and therapeutic target for colorectal cancer.
Photobiocatalysis is a green platform for driving redox enzymatic reactions using solar energy, not needing high‐cost cofactors and redox partners. Here, a visible light‐driven whole‐cell platform for human cytochrome P450 (CYP) photobiocatalysis was developed using natural flavins as a photosensitizer. Photoexcited flavins mediate NADPH/reductase‐free, light‐driven biocatalysis by human CYP2E1 both in vitro and in the whole‐cell systems. In vitro tests demonstrated that the photobiocatalytic activity of CYP2E1 is dependent on the substrate type, the presence of catalase, and the acid type used as a sacificial electron donor. A protective effect of catalase was found against the inactivation of CYP2E1 heme by H2O2 and the direct transfer of photo‐induced electrons to the heme iron not by peroxide shunt. Furthermore, the P450 photobiocatalysis in whole cells containing human CYPs 1A1, 1A2, 1B1, and 3A4 demonstrated the general applicability of the solar‐powered, flavin‐mediated P450 photobiocatalytic system.
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Gut-homing gd T cells are induced by chemokines and cell adhesion molecules and play a critical role in homeostasis and mucosal immunity; however, little is known regarding their upstream regulators. We investigated the role of Axl as a specific regulator of chemokines and cell adhesion molecule in the distribution of intestinal gd T cells. The population of gd T-cell receptor-positive cells including Vg1 and Vg7 subsets was remarkably increased in the intraepithelial lymphocytes of Axl 2/2 mice compared with those of wild-type (WT) mice. An increased number of migrated gd T cells were observed in the coculture with intraepithelial cells from Axl 2/2 mice. The mRNA expression level of chemokine (C-C motif) ligand (CCL) 25 was specifically higher in the small intestine of Axl 2/2 mice than in WT mice. In adoptive transfer, the migration of both thymic and extrathymic gd T cells was increased in Axl 2/2 mice. The activation of Axl signaling down-regulated CCL25 expression via ERK signaling pathway and reduced the population of gd T cells. Systemic dissemination was suppressed in Axl 2/2 mice infected with Salmonella typhimurium. Thus, our findings suggest that Axl plays a critical role in regulating the migration of gd T cells for the maintenance of homeostasis and bacterial resistance.
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