Cancer cells re-program their metabolic machinery to meet the requirements of malignant transformation and progression.
Glutaminase 1 (GLS1) was traditionally known as a mitochondrial
enzyme that hydrolyzes
glutamine into
glutamate and fuels rapid proliferation of
cancer cells. However, emerging evidence has now revealed that GLS1 might be a novel oncogene involved in
tumorigenesis and progression of human
cancers. In this study, we sought to determine whether GLS1 implicated in invasion and
metastasis of
colorectal carcinoma, and its underlying molecular mechanism. By analyzing a large set of clinical data from online datasets, we found that GLS1 is overexpressed in
cancers compared with adjacent normal tissues, and associated with increased patient mortality. Immunohistochemical analysis of GLS1 staining showed that high GLS1 expression is significantly correlated with
lymph node metastasis and advanced clinical stage in
colorectal cancer patients. To investigate the underlying mechanism, we analyzed the
Cancer Genome Atlas database and found that GLS1
mRNA expression is associated with a
hypoxia signature, which is correlated with an increased risk of
metastasis and mortality. Furthermore, reduced
oxygen availability increases GLS1
mRNA and
protein expression, due to transcriptional activation by
hypoxia-inducible factor 1. GLS1 expression in
colorectal cancer cells is required for
hypoxia-induced migration and invasion in vitro and for
tumor growth and metastatic colonization in vivo.