TY - JOUR
TI - Galectin-1 has potential prognostic significance and is implicated in clear cell renal cell carcinoma progression through the HIF/mTOR signaling axis
AU - White, N.M.A.
AU - Masui, O.
AU - Newsted, D.
AU - Scorilas, A.
AU - Romaschin, A.D.
AU - Bjarnason, G.A.
AU - Siu, K.W.M.
AU - Yousef, G.M.
JO - British Journal of Cancer
PY - 2014
VL - 110
TODO - 5
SP - 1250-1259
PB - Nature Publishing Group
SN - 0007-0920, 1532-1827
TODO - 10.1038/bjc.2013.828
TODO - galectin 1;  hypoxia inducible factor;  hypoxia inducible factor 1alpha;  mammalian target of rapamycin;  messenger RNA;  microRNA 22;  mitogen activated protein kinase;  protein kinase B;  protein p70;  proteome;  small interfering RNA;  tumor marker;  small interfering RNA, article;  cancer cell culture;  cancer grading;  cancer prognosis;  cancer size;  cell hypoxia;  cell invasion;  cell migration;  controlled study;  disease free survival;  gene expression;  human;  human cell;  human tissue;  immunohistochemistry;  kidney carcinoma;  major clinical study;  nucleotide sequence;  overall survival;  priority journal;  protein expression;  protein phosphorylation;  signal transduction;  Article;  cancer growth;  tumor invasion;  tumor volume, Carcinoma, Renal Cell;  Cell Line, Tumor;  Cell Movement;  Disease Progression;  Disease-Free Survival;  Galectin 1;  Humans;  Hypoxia-Inducible Factor 1, alpha Subunit;  Kidney Neoplasms;  MicroRNAs;  Mitogen-Activated Protein Kinases;  Phosphorylation;  Prognosis;  Protein Tyrosine Phosphatases;  Proto-Oncogene Proteins c-akt;  Signal Transduction;  TOR Serine-Threonine Kinases
TODO - Background:Metastatic clear cell renal cell carcinoma (ccRCC) patients have <9% 5-year survival rate, do not respond well to targeted therapy and eventually develop resistance. A better understanding of molecular pathways of RCC metastasis is the basis for the discovery of novel prognostic markers and targeted therapies.Methods:We investigated the biological impact of galectin-1 (Gal-1) in RCC cell lines by migration and invasion assays. Effect of Gal-1 expression on the mitogen-activated protein kinase pathway was assessed by proteome array.Results:Increased expression of Gal-1 increased cell migration while knocking down Gal-1 expression by siRNA resulted in reduced cellular migration (P<0.001) and invasion (P<0.05). Gal-1 overexpression increased phosphorylation of Akt, mTOR and p70 kinase. Upon hypoxia and increased HIF-1α, Gal-1 increased in a dose-dependent manner. We also found miR-22 overexpression resulted in decreased Gal-1 and HIF-1α. Immunohistochemistry analysis showed that high Gal-1 protein expression was associated with larger size tumor (P=0.034), grades III/IV tumors (P<0.001) and shorter disease-free survival (P=0.0013). Using the Cancer Genome Atlas data set, we found that high Gal-1 mRNA expression was associated with shorter overall survival (41 vs 78 months; P<0.01).Conclusions:Our data suggest Gal-1 mediates migration and invasion through the HIF-1α-mTOR signaling axis and is a potential prognostic marker and therapeutic target. © 2014 Cancer Research UK.
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