Gastric cancer is one of the most malignant tumor types, and its metastasis is a notable cause of mortality. Among the methods of tumor metastasis, lymphatic metastasis is the predominant one in gastric cancer. A previous study reported that the plasma oxidized low‑density lipoprotein (oxLDL) is the risk factor associated with the development of tumors in patients with abnormal lipid metabolism, but the influence of plasma oxLDL in the lymphatic metastasis of gastric cancer remains unclear. In the present study, the concentration of plasma oxLDL from patients with gastric cancer was detected with an ELISA kit, and the lymphatic vessel density in gastric cancer tissues was determined by D2‑40 staining. The correlation analysis of oxLDL concentration and lymphatic vessel density demonstrated that plasma oxLDL was positively correlated with lymphatic metastasis in patients with gastric cancer. Subsequently, the popliteal lymph node metastasis animal experiment with nude mice confirmed that oxLDL could promote the lymphatic metastasis of gastric cancer. Following this, the western blotting and ELISA data demonstrated that oxLDL promoted the expression and secretion of vascular endothelia growth factor (VEGF)‑C in gastric cancer cell lines. Finally, blocking the lectin‑like oxLDL‑1 (LOX‑1) receptor, a specific receptor for oxLDL, and the nuclear factor (NF)‑κB signaling pathway following oxLDL (50 µg/ml) treatment in HGC‑27 cells revealed that oxLDL could activate the NF‑κB signaling pathway mediated by LOX‑1, with subsequent upregulation of VEGF‑C expression, and secretion in and from gastric cancer cells, and finally that it could promote the lymphatic metastasis of gastric cancer. These data indicate the association between the plasma oxLDL and the lymphatic metastasis of gastric cancer, and indicate that oxLDL elimination may be a potential therapeutic target for the prevention and intervention of early lymph node metastasis in gastric cancer.

Kallistatin has been recognized as an endogenous angiogenic inhibitor. However, its effects on lymphatic endothelial cells and lymphangiogenesis remain poorly understood. Lymphangiogenesis is involved in tumor metastasis via the lymphatic vasculature in various types of tumors. The aim of this study was to investigate the effects of kallistatin on lymphangiogenesis and the mechanism of action involved. Treatment with kallistatin recombinant protein or overexpression of kallistatin inhibited the proliferation, migration and tube formation of human lymphatic endothelial cells (hLECs), and induced apoptosis of hLECs. Furthermore, our results showed that the lymphatic vessel density (LVD) was reduced in lung and stomach sections from kallistatin-overexpressing transgenic mice. Treatment with kallistatin recombinant protein decreased the LVD in the implanted gastric xenograft tumors of nude mice. To the best of our knowledge, the present study is the first to demonstrate that kallistatin possesses anti-lymphangiogenic activity in vitro and in vivo. Moreover, kallistatin inhibited proliferation and migration of hLECs by reducing the phosphorylation of ERK and Akt, respectively. These findings suggested that kallistatin may be a promising agent that could be used to suppress cancer metastasis by inhibiting both angiogenesis and lymphangiogenesis.

Accumulating evidence suggests the pivotal role of the sympathetic nervous system in the initiation and aggressive progression of tumors, whereas the role of β‑adrenergic receptor (β‑AR) signaling in neuroblastoma (NB) and the underlying regulatory mechanisms have not yet been well elucidated. In the present study, it was demonstrated that the expression of both β1‑AR and β2‑AR was significantly increased in clinical samples of NB compared with those of ganglioneuroma (GN) and ganglioneuroblastoma (GNB), and that β2‑AR is the key β‑adrenergic receptor responsible for NB cell growth. Further investigation showed that the expression levels of the autophagy markers LC3‑Ⅱ, beclin‑1 and unc‑51‑like autophagy kinase 1 (ULK1) were also elevated in NB, compared to the cases of GN and GNB. Moreover, β2‑AR expression was found to be positively associated with autophagy markers in the clinical NB specimens. Cellular functional assays demonstrated that β2‑AR activation promoted NB cell growth and activated the autophagy pathway. Pharmacological inhibition of autophagy with 3‑methyladenine abolished β2‑AR‑induced NB cell growth. Mechanistically, β2‑AR signaling triggers autophagy through CREB‑mediated ULK1 upregulation. In conclusion, the present study uncovered a novel regulatory mechanism of β2‑AR‑activated autophagy in NB cell growth and provides a novel potential therapeutic approach for treating NB by targeting autophagy and the β2‑AR pathway.

Abnormal lipid metabolism is the sign of tumour cells. Previous researches have revealed that the lipolytic pathway may contribute to the progression of colorectal cancer (CRC). However, adipose triglyceride lipase (ATGL) role in CRC cells remains unclear. Here, we find that elevated ATGL positively correlates with CRC clinical stages and negatively associates with overall survival. Overexpression of ATGL significantly promotes CRC cell proliferation, while knockdown of ATGL inhibits the proliferation and promotes the apoptosis of CRC cells in vitro. Moreover, in vivo experiments, ATGL promotes the growth of CRC cells. Mechanistically, ATGL enhances the carcinogenic function of CRC cells via promoting sphingolipid metabolism and CoA biosynthesis pathway-related gene levels by degrading triglycerides, which provides adequate nutrition for the progression of CRC. Our researches clarify for the first time that ATGL is a novel oncogene in CRC and may provide an important prognostic factor and therapeutic target for CRC.

Neuroblastoma (NB) is one of the deadliest paediatric solid tumours due to its rapid proliferative characteristics. Amplified copies of MYCN are considered the most important marker for the prediction of tumour relapse and progression in NB, but they were only detected in 20-30% of NB patients, indicating there might be other oncogenes in the development of NB. The far upstream element binding protein 1 (FUBP1) was first identified as a transcriptional regulator of the proto-oncogene MYC. However, the expression and role of FUBP1 in NB have not been documented.

Effective biomarkers for the diagnosis of colorectal cancer (CRC) are essential for improving prognosis. Imbalance in regulation of N6-methyladenosine (m6A) RNA has been associated with a variety of cancers. However, whether the m6A RNA levels of peripheral blood can serve as a diagnostic biomarker for CRC is still unclear. In this research, we found that the m6A RNA levels of peripheral blood immune cells were apparently elevated in the CRC group compared with those in the normal controls (NCs) group. Furthermore, the m6A levels arose as CRC progressed and metastasized, while these levels decreased after treatment. The area under the curve (AUC) of the m6A levels was 0.946, which was significantly higher than the AUCs for carcinoembryonic antigen (CEA; 0.817), carbohydrate antigen 125 (CA125; 0.732), and carbohydrate antigen 19-9 (CA19-9; 0.771). Moreover, the combination of CEA, CA125, and CA19-9 with m6A levels improved the AUC to 0.977. Bioinformatics and qRT-PCR analysis further confirmed that the expression of m6A modifying regulator IGF2BP2 was markedly elevated in peripheral blood of CRC patients. Gene set variation analysis (GSVA) implied that monocyte was the most abundant m6A-modified immune cell type in CRC patients' peripheral blood. Additionally, m6A modifications were negatively related to the immune response of monocytes. In conclusion, our results revealed that m6A RNA of peripheral blood immune cells was a prospective non-invasive diagnostic biomarker for CRC patients and might provide a valuable therapeutic target.

Nasopharyngeal carcinoma (NPC) is one of the most malignant tumors in southern China and Asia, and lymph node metastasis is an important cause for treatment failure. Lymphangiogenesis is a crucial step in lymphatic metastasis of NPC, while little is known about lymphangiogenesis in NPC. Similar to angiogenesis, lymphangitic neovascularization is a process of balance between pro-lymphangiogenesis and anti-lymphangiogenesis factors, but there are few studies on endogenous lymphangiogenesis inhibitors. Pigment epithelium-derived factor (PEDF) is a well-known effective endogenous angiogenesis inhibitor. However, the relationship between PEDF and lymphangiogenesis remains unknown. Our present study reveals that PEDF is lowly expressed in human NPC tissues with poor prognosis and is negatively correlated with lymphatic vessel density (LVD). Consistently, PEDF inhibits lymphangiogenesis and lymphatic metastasis of NPC in vivo experiments. Mechanistically, PEDF inhibits the proliferation, migration, and tube formation of lymphatic endothelial cells and promotes cell apoptosis. On the other hand, PEDF reduces the expression and secretion of vascular endothelial growth factor C (VEGF-C) of NPC cells through the nuclear factor-κB (NF-κB) signaling pathway. Our findings indicate that PEDF plays a vital role in lymphatic metastasis by targeting both lymphatic endothelial cells and NPC cells, and PEDF may represent a novel therapeutic target for NPC.