Studies indicate that the chemokine receptor is responsible for poor prognosis of hepatocellular carcinoma (HCC) patients. In this study, we initially demonstrated that CCR4 is overexpressed in HCC specimens, and its elevation in HCC tissues positively correlates with tumor capsule breakthrough and vascular invasion. Although overexpression of CCR4 failed to influent proliferation of HCC cells in vitro apparently, the prominent acceleration on HCC tumor growth in vivo was remarkable. The underlying mechanism may be involved in neovascularization. Interestingly, different from effect on proliferation, CCR4 overexpression could trigger HCC metastasis both in vitro and in vivo also induced HCC cell epithelial-mesenchymal transition (EMT) as well. Then we identified matrix metalloproteinase 2 (MMP2) as a direct target of CCR4 which plays an important role in CCR4-mediated HCC cell invasion, which was up-regulated by ERK/AKT signaling. Positive correlation between CCR4 and MMP2 expression was also observed in HCC tissues. In conclusion, our study suggested that chemokine receptor CCR4 promotes HCC malignancy and facilitated HCC cell metastases via ERK/AKT/MMP2 pathway. These findings suggest that CCR4 may be a potential new diagnostic and prognostic marker in HCC, and targeting CCR4 may be a potential therapeutic option for blocking HCC metastasis.

Tumor metastasis is the leading cause of death in patients with advanced gastric cancer (GC). Limited therapeutic regimens are available for this condition, which is associated with a poor prognosis, and the mechanisms underlying tumor metastasis remain unclear. In the present study, increased histone methyltransferase G9A expression in GC tissues correlated with advanced stage and shorter overall survival, and in vitro and in vivo experiments revealed that G9A promoted tumor invasion and metastasis. Moreover, we observed that Reg IV induced G9A via the p-ERK/p-SP1 pathway. SP1 directly binds the G9A promoter and enhances G9A expression, and upregulated G9A then forms a transcriptional activator complex with P300 and GR, thereby promoting ITGB3 expression induced by dexamethasone (DEX) and contributing to GC metastasis. However, the G9A-mediated increase in ITGB3 expression was not dependent on the SET domain and methyltransferase activity of G9A. This study demonstrates that G9A is an independent prognostic marker and promotes metastasis in GC, thus suggesting that it may be a tumor biomarker and potential therapeutic target in GC.

No abstract

We theoretically investigate high-order harmonic generation (HHG) from solids in two-color fields. It is found that under the premise of maintaining the same amplitude, the intensity of the second plateau can be enhanced by two to three orders in a proper two-color field compared with the result in the monochromatic field with the same frequency as the driving pulse of the two-color field. This can be attributed to the fact that most excited electrons can be driven to the top of the first conduction band due to the larger vector potential of the two-color fields, which leads to the higher electron population of upper conduction bands. Moreover, we also find that isolated attosecond pulses can be generated from solids by choosing a proper two-color field that allows the electrons to reach the top of the first conduction band only once. This work provides a promising method for extending the range of solid HHG spectra in experiments.

Asporin has been implicated as an oncogene in various types of human cancers; however, the roles of asporin in the development and progression of colorectal cancer (CRC) have not yet been determined. With clinical samples, we found that asporin was highly expressed in CRC tissues compared to adjacent normal tissues and the asporin expression levels were significantly associated with lymph node metastasis status and TNM stage of the patients. Through knockdown of asporin in CRC cell lines RKO and SW620 or overexpression of asporin in cell lines HT-29 and LoVo, we found that asporin could enhance wound healing, migration and invasion abilities of the CRC cells. Further more, with the human umbilical vein endothelial cells (HUVECs) tube formation assays and the xenograft model, we found that asporin promoted the tumor growth through stimulating the VEGF signaling pathway. The portal vein injection models suggested that asporin overexpression stimulated the liver metastasis of HT29 cell line, while asporin knockdown inhibited the liver metastasis of RKO cell line. In addition, asporin was found to augment the phosphorylation of EGFR/Src/cortactin signaling pathway, which might be contributed to the biological functions of asporin in CRC metastasis. These results suggested that asporin promoted the tumor growth and metastasis of CRC, and it could be a potential therapeutic target for CRC patients in future.

Leukemia inhibitory factor receptor (LIFR) has been documented as a cancer promoter and to be present at high levels in various types of tumor tissues. In our search for molecules prognostic of colorectal cancer (CRC), we found high levels of LIFR in CRC tissue samples. Further analyses revealed that LIFR was indeed prognostic of CRC patient survival, and was associated with tumor size, lymphatic metastasis and stages. LIFR was found to promote tumor growth, metastasis and angiogenesis both in vitro and in vivo. High levels of LIFR in CRC facilitated proliferation and migration of endothelial cells, resulting in an increase in angiogenic activity. Moreover, interleukin 8 (IL-8) was found to play a role in the LIFR induced angiogenesis. IL-8 levels were correlated with LIFR levels in CRC tissues, whereas depletion of IL-8 led to a reduced angiogenic activity of LIFR in CRC cells. In addition, LIFR increased phosphorylation level of Erk, which regulates il-8 transcription. We conclude that LIFR is possibly a valuable prognostic marker for CRC. Our results also implicate a mechanism by which LIFR regulates tumor angiogenesis through Erk/IL-8 pathway, and that LIFR could be a potential therapeutic target for CRC.

Our findings suggest that genetic variants in the RBP4 gene may be associated with circulating RBP4 concentration and phenotypes related to glucose metabolism.

Hydroxyl radicals (•OH) generated in the photocatalytic process are crucial to the conversion of methane (CH4) to value-added methanol (CH3OH) at room temperature. However, utilizing noble metal-free catalysts and low-energy photons of solar light, such as visible and near-infrared light (vis–NIR), is difficult to provide more electron states to form •OH radicals. Here, we developed FeOOH/Li0.1WO3 core–shell nanorods via a two-step in/out co-modification of hexagonal tungsten oxide (h-WO3): (1) lithium ions intercalating into the hexagonal tunnels of h-WO3 to form Li0.1WO3 nanorods and (2) using FeOOH-wrapped Li0.1WO3 to obtain FeOOH/Li0.1WO3 core–shell nanorods. Introduction of lithium induces polaron transition in Li0.1WO3, enabling the absorption of vis-NIR light. Interestingly, FeOOH-based Fenton-like reaction when H2O2 is selected as an oxidant favors the generation of more •OH radicals available for CH4 oxidation to CH3OH. Meanwhile, FeOOH with FeIII as an “electron sink” highly improves the separation of photoinduced electrons and holes in Li0.1WO3. Eventually, efficient selective formation of CH4OH is achieved with remarkable generation rates up to ∼342 and ∼160 μmol g–1 at visible light (420–700 nm) and NIR light (≥800 nm), respectively. Our finding opens up new possibilities for developing noble metal-free catalysts for solar energy-driven CH4 conversion to CH3OH under ambient conditions.