Roles of galectin-3 in the tumor microenvironment and tumor metabolism
ONCOLOGY REPORTS
Authors: Guo, Yanan; Shen, Rong; Yu, Linghui; Zheng, Xin; Cui, Rong; Song, Yanfeng; Wang, Degui
Abstract
Galectin-3 is expressed in various tissues and plays an important role in the tumor microenvironment (TME). Galectin-3 has been found to be overexpressed in a variety of cancers and is associated with tumor progression and metastasis. Over the past decades, emerging evidence has suggested that the TME may induce galectin-3 expression to maintain cellular homeostasis and promote cell survival. Furthermore, galectin-3 regulates immune cell function to promote tumor-driven immunosuppression through several mechanisms. In the TME, intracellular and extracellular galectin-3 has different functions. In addition, it has been reported that galectin-3 is associated with glycolysis and mitochondrial metabolism in tumors, and it is involved in the regulation of relevant signaling pathways, thus promoting cancer cell survival via adapting to the TME. The aim of the present review was to summarize the current knowledge on galectin-3 production and its function in the TME, its effect on TME immunosuppression, its association with tumor metabolism and relevant signaling pathways, and to report common types of cancer in which galectin-3 is highly expressed, in order to ensure a comprehensive understanding of the critical effects of galectin-3 on tumor progression and metastasis.
Characterisation of the teleostean kappa B-Ras family: The two members NKIRAS1 and NKIRAS2 from rainbow trout influence the activity of NF-kappa B in opposite ways
FISH & SHELLFISH IMMUNOLOGY
Authors: Sarais, Fabio; Rebl, Henrike; Verleih, Marieke; Ostermann, Sven; Krasnov, Aleksei; Kollner, Bernd; Goldammer, Tom; Rebl, Alexander
Abstract
Two structurally similar NF-kappa B-inhibitor-interacting Ras-like proteins (NKIRAS) regulate the activity of the transcription factor NF-kappa B and thereby control several early immune mechanisms in mammals. We identified the orthologous sequences of NKIRAS1 and NKIRAS2 from the rainbow trout Oncorhynchus mykiss. The level of sequence identity was similarly high (>= 68%) between the two and in comparison to their mammalian counterparts. Strikingly, NKIRAS2 was present as four transcript variants. These variants differed only in length and in the nucleotide composition of their 5' termini and were most likely generated by splicing along unconventional splice sites. The shortest NKIRAS2 variant was most strongly expressed in a lymphocyte-enriched population, while NKIRAS1 was most strongly expressed in cells of myeloid origin. Fluorescent-labelled NKIRAS1 and NKIRAS2 proteins from rainbow trout were detected in close association with the p65 subunit of NF-kappa B in the nucleus and cytoplasm of CHSE-214 cells. Subsequent reporter-gene experiments revealed that NKIRAS1 and a longer NKIRAS2 variant in rainbow trout decreased the level of activated NF-kappa B, while the two shortest NKIRAS2 variants increased the NF-kappa B activity. In addition, the overexpression of the shortest NKIRAS2 variant in CHSE-214 cells induced a stronger transcription of the genes encoding the pro-inflammatory cytokines TNF, CXCL8, and IL1B compared to non-transfected control cells. This is the first characterisation of NKIRAS orthologues in bony fish and provides additional information to the as yet underexplored inhibition pathways of NF-kappa B in lower vertebrates.