Role of Notch, IL‑1 and leptin expression in colorectal cancer

Abstract

An increasing number of studies have shown that angiogenesis has an important role in the progression of cancer. The growth of a new network of blood vessels is crucial for tumor growth and metastasis, which is promoted by several proangiogenic factors. Leptin, an essential adipokine that is secreted from fat tissue, is one of these pro-angiogenic factors. It has been shown that the inhibition of leptin-induced angiogenesis resulted in decreased levels of vascular endothelial growth factor (VEGF)/VEGFR2, hypoxia inducible factor (HIF) 1α, NF-κB, IL-1 and Notch and reduced the tumor growth in breast cancer. Leptin induces angiogenesis in breast cancer either by upregulating VEGFR2 in endothelial cells or by increasing VEGF/VEGFR2 expression through the Notch, IL-1 and leptin crosstalk outcome (NILCO) pathway. NILCO is a novel mechanism that interacts with proinflammatory and proangiogenic signals, which are critical for cell proliferation and angiogenesis in cancer. Several studies have shown that components of NILCO may affect human cancer incidence and progression. However, to the best of our knowledge, the interactions between Notch, IL-1 and leptin in human colorectal cancer have not been yet studied at the molecular level. The aim of the present study was to investigate the expression levels of genes related to the NILCO pathway in human colorectal cancer specimens. The current results demonstrated that leptin, leptin receptor (ObR) b, Notch-1, Notch-4, IL-1α, IL-1β, IL-1R, IL-6, JAK-2, STAT-1, STAT-3, VEGFA, VEGFR1, VEGFR2, TNF-α and NF-κB mRNA expression levels in the cancer tissue were increased compared with the normal tissue. No significant changes in the mRNA expression levels of Jagged-1, HIF-1α and TNF receptor 1 were observed. Western blotting revealed that the protein expression levels of IκB were increased in the cancer tissue compared with normal tissue, whereas HIF-1α and phosphorylated STAT-1 levels were decreased. IL-6 and VEGFA plasma concentrations were statistically raised and the leptin plasma concentration was also raised, although significantly, patients with cancer compared with control individuals. Together, the present findings indicated that Notch, IL-1 and leptin may serve a crucial role in the development of colorectal cancer.

Cardiac rehabilitation may influence leptin and VEGF A crosstalk in patients after acute coronary syndrome

“…Also, leptin increases VEGF/VEGF R2 expression via the up-regulation of Notch and IL1, forming the Notch, IL1 and leptin cross-talk outcome (NILCO) pathway. Moreover, leptin induces the expression of Notch1-4/Jagged-1/delta-like canonical Notch ligand (Dll) 4, which plays an important role in Notch signalling pathway 33 , 51 , 52 . Furthermore, some studies indicated, that IL1 activates Notch signalling through NfkB activity 53 and leptin up-regulates IL1 via an NfkB-dependent mechanism 32 .…”

LY6G6D is Epigenetically Activated in Classical Colorectal Adenocarcinoma and Hyper-Methylated in Mucinous Subtypes Determining Resistance to FOLFOX Therapeutic Regimens.

“…1D). In addition, to the well-known upregulation of genes involved in mucin processing and secretion such as MUC2, over representation analysis of the common upregulated genes revealed a prominent activation of in ammatory chemokines such as CXC motif chemokine ligand (CXCL) 8, CXCR1 and CXCR2 receptor and IL-1β in ammosome [27] (Fig. 2A).…”

Lymphocyte antigen 6G6D-mediated modulation through p38α MAPK and DNA methylation in colorectal cancer

“…1D). In addition to the well-known MUC2 gene involved in mucin processing and secretion, analysis of the upregulated genes revealed pathways not previously known to be overexpressed in mucin cancer, including inflammatory chemokines such as CXC motif chemokine ligand (CXCL) 8, CXCR1 and CXCR2 receptor, and IL -1β-inflammosome [30] (Fig. 2A).…”