Lipocalin 2 Antagonizes the Proangiogenic Action of Ras in Transformed Cells

Venkatesha, Shivalingappa; Hanai, Jun‐ichi; Seth, Pankaj; Karumanchi, S. Ananth; Sukhatme, Vikas P.

doi:10.1158/1541-7786.mcr-06-0110

Cited by 31 publications

(32 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2 In malignant RAS-transformed cells, Lipocalin-2 induced an epithelial phenotype, blocking their capacity for growth, invasiveness, and metastasization. 11,25 In our study, Sw620 and Hct116 cells that included the K-ras mutations were sensitive to ZD55-Lipocalin-2, especially Sw620 cells in vivo. As such, ZD55-Lipocalin-2 may be a promising agent for treating colorectal cancer that is resistant to chemotherapy.…”

Section: Discussionmentioning

confidence: 51%

“…Some studies have demonstrated that Lipocalin-2 has antitumor and antimetastatic effects in some neoplasias, such as cancer from the colon, ovary, and pancreas, due to its inhibition of the proneoplastic protein hypoxia-inducible factor 1, FA-Kinase phosphorylation, and vascular endothelial growth factor (VEGF) synthesis. [8][9][10][11][12] Apoptosis induced by Lipocalin-2 in cells was also reported, 13,14 but not in colorectal cancer cells. Moreover, there is no direct evidence showing therapeutic effects of Lipocalin-2 in colorectal cancer.…”

Section: Introductionmentioning

confidence: 77%

See 1 more Smart Citation

One Potential Oncolytic Adenovirus Expressing Lipocalin-2 for Colorectal Cancer Therapy

Zheng²,

Feng³

et al. 2013

Cancer Biotherapy and Radiopharmaceuticals

View full text Add to dashboard Cite

Colorectal cancer is an aggressive malignancy with a high mortality rate; however, effective therapies are currently lacking. Cancer-targeting gene-virotherapy (CTGVT) has been proposed to be a promising strategy for cancer therapy. The purpose of this study was to investigate the antitumor activity of the oncolytic adenovirus harboring Lipocalin-2 (ZD55-Lipocalin-2, an example of CTGVT) in colorectal cancer. ZD55-Lipocalin-2 was generated by deleting E1B55-KD and inserting the Lipocalin-2 gene. Its cytopathic effects and cell growth inhibition were detected in vitro, and antitumor effects were examined in a nude mouse model of human colorectal cancer xenografts. Results showed that ZD55-Lipocalin-2 significantly inhibited the colorectal cancer growth by selective cytolysis, inducing apoptosis and decreasing the microvessel density in tumors. The anticancer potential of ZD55-Lipocalin-2 showed stronger than that of the isolated Lipocalin-2 gene therapy or isolated ZD55 oncolytic adenovirus therapy. ZD55-Lipocalin-2 may serve as a potential anticancer agent for colorectal cancer treatment.

show abstract

Section: Discussionmentioning

confidence: 51%

Section: Introductionmentioning

confidence: 77%

One Potential Oncolytic Adenovirus Expressing Lipocalin-2 for Colorectal Cancer Therapy

Zheng²,

Feng³

et al. 2013

Cancer Biotherapy and Radiopharmaceuticals

View full text Add to dashboard Cite

show abstract

“…Some of the anticancer properties of NGAL are due to its ability to inhibit the expression of hypoxia inducible factor-1a (HIF-1a) dependent synthesis of vascular endothelial growth factor (VEGF) [104]. Also NGAL can inhibit and phosphorylation of focal adhesion kinase (FAK) and…”

Section: Effects Of Ngal On Cancer Progressionmentioning

confidence: 99%

Roles of NGAL and MMP-9 in the tumor microenvironment and sensitivity to targeted therapy

Candido

Abrams

Steelman

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

View full text Add to dashboard Cite

Various, diverse molecules contribute to the tumor microenvironment and influence invasion and metastasis. In this review, the roles of neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9) in the tumor microenvironment and sensitivity to therapy will be discussed. The lipocalin family of proteins has many important functions. For example when NGAL forms a complex with MMP-9 it increases its stability which is important in cancer metastasis. Small hydrophobic molecules are bound by NGAL which can alter their entry into and efflux from cells. Iron transport and storage are also influenced by NGAL activity. Regulation of iron levels is important for survival in the tumor microenvironment as well as metastasis. Innate immunity is also regulated by NGAL as it can have bacteriostatic properties. NGAL and MMP-9 expression may also affect the sensitivity of cancer cells to chemotherapy as well as targeted therapy. Thus NGAL and MMP-9 play important roles in key processes involved in metastasis as well as response to therapy. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza.

show abstract

“…Markedly induced genes common to all three arrays included Lcn2 (lipocalin 2) and MT2 (metallothionein 2), which are multifunctional iron-binding proteins. [23][24][25] Highly downregulated transcripts shared by each include Clec4f (C-type lectin domain family 4, member F) and Tm9sf2 (transmembrane 9 superfamily member 2), which are poorly characterized genes putatively involved in carbohydrate binding and endosome function, respectively. 26,27 Notably, a number of highly regulated genes were differentially affected by the D-type cyclins.…”

Section: Induction Of Hepatocyte Proliferation By the D-type Cyclinsmentioning

confidence: 99%

Distinct proliferative and transcriptional effects of the D-type cyclins in vivo

Mullany¹,

White²,

Hanse³

et al. 2008

Cell Cycle

View full text Add to dashboard Cite

The D-type cyclins (D1, D2 and D3) are components of the cell cycle machinery and govern progression through G 1 phase in response to extracellular signals. Although these proteins are highly homologous and conserved in evolution, they contain distinct structural motifs and are differentially regulated in various cell types. Cyclin D1 appears to play a role in many different types of cancer, whereas cyclins D2 and D3 are less frequently associated with malignancy. In this study, we transiently expressed cyclin D1, D2 or D3 in hepatocytes and analyzed transcriptional networks regulated by each. All three D-type cyclins promoted robust hepatocyte proliferation and marked liver growth, although cyclin D3 stimulated less DNA synthesis than D1 or D2. Accordingly, the three D-type cyclins similarly activated genes associated with cell division. Cyclin D1 regulated transcriptional pathways involved in the metabolism of carbohydrates, lipids, amino acids, and other substrates, whereas cyclin D2 did not regulate these pathways despite having an equivalent effect on proliferation. Comparison of transcriptional profiles following 70% partial hepatectomy and cyclin D1 transduction revealed a highly significant overlap, suggesting that cyclin D1 may regulate diverse cellular processes in the regenerating liver. In summary, these studies provide the first comparative analysis of the transcriptional networks regulated by the D-type cyclins and provide insight into novel functions of these key cell cycle proteins. Further study of the unique targets of cyclin D1 should provide further insight into its prominent role in proliferation, growth and cancer.

show abstract

Lipocalin 2 Antagonizes the Proangiogenic Action of Ras in Transformed Cells

Cited by 31 publications

References 53 publications

One Potential Oncolytic Adenovirus Expressing Lipocalin-2 for Colorectal Cancer Therapy

One Potential Oncolytic Adenovirus Expressing Lipocalin-2 for Colorectal Cancer Therapy

Roles of NGAL and MMP-9 in the tumor microenvironment and sensitivity to targeted therapy

Distinct proliferative and transcriptional effects of the D-type cyclins in vivo

Contact Info

Product

Resources

About