Galectin-1 Has Potential Prognostic Significance and is Implicated in Clear Cell Renal Cell Carcinoma Progression Through the HIF/mTOR Signaling Axis

Overview

Journal Br J Cancer

Specialty Oncology

Date 2014 Feb 6

PMID 24496460

Citations 36

Authors

N M A White

O Masui

D Newsted

A Scorilas

A D Romaschin

G A Bjarnason

K W M Siu

G M Yousef

Affiliations

Soon will be listed here.

Abstract

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.

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References

Chiang W, Liu S, Fang L, Lin C, Wu M, Chen Y . Overexpression of galectin-1 at the tumor invasion front is associated with poor prognosis in early-stage oral squamous cell carcinoma. Oral Oncol. 2007; 44(4):325-34. DOI: 10.1016/j.oraloncology.2007.03.004. View

Brandt B, Abou-Eladab E, Tiedge M, Walzel H . Role of the JNK/c-Jun/AP-1 signaling pathway in galectin-1-induced T-cell death. Cell Death Dis. 2011; 1:e23. PMC: 3032336. DOI: 10.1038/cddis.2010.1. View

Wu H, Chen P, Liao R, Li Y, Yi Y, Wang J . Overexpression of galectin-1 is associated with poor prognosis in human hepatocellular carcinoma following resection. J Gastroenterol Hepatol. 2012; 27(8):1312-9. DOI: 10.1111/j.1440-1746.2012.07130.x. View

Barondes S, Castronovo V, Cooper D, Cummings R, Drickamer K, Feizi T . Galectins: a family of animal beta-galactoside-binding lectins. Cell. 1994; 76(4):597-8. DOI: 10.1016/0092-8674(94)90498-7. View

Zhao X, Chen T, Xia L, Guo M, Xu Y, Yue F . Hypoxia inducible factor-1 mediates expression of galectin-1: the potential role in migration/invasion of colorectal cancer cells. Carcinogenesis. 2010; 31(8):1367-75. DOI: 10.1093/carcin/bgq116. View

Laderach D, Gentilini L, Giribaldi L, Delgado V, Nugnes L, Croci D . A unique galectin signature in human prostate cancer progression suggests galectin-1 as a key target for treatment of advanced disease. Cancer Res. 2012; 73(1):86-96. DOI: 10.1158/0008-5472.CAN-12-1260. View

Rosner M, Siegel N, Valli A, Fuchs C, Hengstschlager M . mTOR phosphorylated at S2448 binds to raptor and rictor. Amino Acids. 2009; 38(1):223-8. DOI: 10.1007/s00726-008-0230-7. View

Romaniuk M, Croci D, Lapponi M, Tribulatti M, Negrotto S, Poirier F . Binding of galectin-1 to αIIbβ₃ integrin triggers "outside-in" signals, stimulates platelet activation, and controls primary hemostasis. FASEB J. 2012; 26(7):2788-98. DOI: 10.1096/fj.11-197541. View

Diamandis M, White N, Yousef G . Personalized medicine: marking a new epoch in cancer patient management. Mol Cancer Res. 2010; 8(9):1175-87. DOI: 10.1158/1541-7786.MCR-10-0264. View

10.

Saussez S, Decaestecker C, Lorfevre F, Cucu D, Mortuaire G, Chevalier D . High level of galectin-1 expression is a negative prognostic predictor of recurrence in laryngeal squamous cell carcinomas. Int J Oncol. 2007; 30(5):1109-17. View

11.

Kim H, Do I, Jeon H, Cho Y, Park Y, Choi J . Galectin 1 expression is associated with tumor invasion and metastasis in stage IB to IIA cervical cancer. Hum Pathol. 2012; 44(1):62-8. DOI: 10.1016/j.humpath.2012.04.010. View

12.

Khella H, White N, Faragalla H, Gabril M, Boazak M, Dorian D . Exploring the role of miRNAs in renal cell carcinoma progression and metastasis through bioinformatic and experimental analyses. Tumour Biol. 2011; 33(1):131-40. DOI: 10.1007/s13277-011-0255-5. View

13.

Lee M, Han H . Galectin-1 upregulates glucose transporter-1 expression level via protein kinase C, phosphoinositol-3 kinase, and mammalian target of rapamycin pathways in mouse embryonic stem cells. Int J Biochem Cell Biol. 2008; 40(11):2421-30. DOI: 10.1016/j.biocel.2008.04.004. View

14.

Ho V, BUNN H . Effects of transition metals on the expression of the erythropoietin gene: further evidence that the oxygen sensor is a heme protein. Biochem Biophys Res Commun. 1996; 223(1):175-80. DOI: 10.1006/bbrc.1996.0865. View

15.

Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C . Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007; 370(9605):2103-11. DOI: 10.1016/S0140-6736(07)61904-7. View

16.

Jung T, Jung S, Ryu H, Jeong Y, Jin Y, Jin S . Role of galectin-1 in migration and invasion of human glioblastoma multiforme cell lines. J Neurosurg. 2008; 109(2):273-84. DOI: 10.3171/JNS/2008/109/8/0273. View

17.

Lee M, Lee S, Park J, Han H . Interaction of galectin-1 with caveolae induces mouse embryonic stem cell proliferation through the Src, ERas, Akt and mTOR signaling pathways. Cell Mol Life Sci. 2009; 66(8):1467-78. PMC: 11131554. DOI: 10.1007/s00018-009-8691-8. View

18.

Fischer I, Weber M, Kuhn C, Fitzgerald J, Schulze S, Friese K . Is galectin-1 a trigger for trophoblast cell fusion?: the MAP-kinase pathway and syncytium formation in trophoblast tumour cells BeWo. Mol Hum Reprod. 2011; 17(12):747-57. DOI: 10.1093/molehr/gar053. View

19.

Croci D, Salatino M, Rubinstein N, Cerliani J, Cavallin L, Leung H . Disrupting galectin-1 interactions with N-glycans suppresses hypoxia-driven angiogenesis and tumorigenesis in Kaposi's sarcoma. J Exp Med. 2012; 209(11):1985-2000. PMC: 3478924. DOI: 10.1084/jem.20111665. View

20.

Jung E, Moon H, Cho B, Jeong C, Joo Y, Lee Y . Galectin-1 expression in cancer-associated stromal cells correlates tumor invasiveness and tumor progression in breast cancer. Int J Cancer. 2007; 120(11):2331-8. DOI: 10.1002/ijc.22434. View