Τίτλος:
Galectin-1 has potential prognostic significance and is implicated in clear cell renal cell carcinoma progression through the HIF/mTOR signaling axis
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
White, N.M.A.
Masui, O.
Newsted, D.
Scorilas, A.
Romaschin, A.D.
Bjarnason, G.A.
Siu, K.W.M.
Yousef, G.M.
Περιοδικό:
British Journal of Cancer
Εκδότης:
Nature Publishing Group
Λέξεις-κλειδιά:
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
DOI:
10.1038/bjc.2013.828
