The Role of Lysyl Oxidase in SRC-Dependent Proliferation and Metastasis of Colorectal Cancer

Baker, Ann‐Marie; Cox, Thomas R.; Bird, Dennis K.; Lang, Georgina; Murray, Graeme I.; Sun, Xiao‐Feng; Southall, Stacey M.; Wilson, J.; Erler, Janine T.

doi:10.1093/jnci/djq569

Cited by 177 publications

(211 citation statements)

References 53 publications

Supporting

Mentioning

193

Contrasting

Unclassified

Order By: Relevance

“…18 We mainly used this pair of cell lines in this study, because they had the same genetic background with different metastatic potential. 19 To evaluate their metastatic activities in vivo, we performed the orthotopic transplantation model of CRC metastasis in mice 6,17,20 with the use of GFP marker. After injecting the cells into the rectal smooth muscle layer of nude mice, we macroscopically examined metastatic foci using GFP fluorescence.…”

Section: Cancer Cell Biologymentioning

confidence: 99%

The role of CXCR3 and CXCR4 in colorectal cancer metastasis

Murakami

Kawada

Iwamoto

et al. 2012

Intl Journal of Cancer

115

View full text Add to dashboard Cite

Chemokines and their receptors play key roles in leukocyte trafficking and are also implicated in cancer metastasis. We previously demonstrated that forced expression of CXCR3 promotes colon cancer metastasis preferentially to the draining lymph nodes (LNs), with poor prognosis. Using clinical colorectal cancer (CRC) samples, here, we show that expressions of CXCR3 and CXCR4 are significantly higher in metastatic foci within LNs and liver compared to primary tumors, whereas ligands for CXCR3 and CXCR4 are not. We also have demonstrated that some human CRC cell lines constitutively express both CXCR3 and CXCR4, and that activation of CXCR3 strengthens the CXCR4‐mediated cell migration in vitro in a synergistic manner. By constructing SW620 cell lines with reduced expression of CXCR3 and/or CXCR4 using microRNA, we investigated in vivo metastatic activities in a mouse rectal transplantation model. Six weeks after inoculation, CXCR3‐, CXCR4‐, and CXCR3/CXCR4 double‐knockdowns significantly reduced metastasis to LNs, liver and lungs, compared to the control (p < 0.05). Importantly, its suppressive effect on LN metastasis was significantly stronger in CXCR3‐ and CXCR3/CXCR4 double‐knockdowns. In addition, CXCR3‐ and CXCR3/CXCR4 double‐knockdowns significantly decreased the dissemination of cancer cells to liver and lungs, even after 2 weeks. These results indicate that targeting CXCR3 and CXCR4 can be a promising therapy against CRC metastasis.

show abstract

Section: Cancer Cell Biologymentioning

confidence: 99%

The role of CXCR3 and CXCR4 in colorectal cancer metastasis

Murakami

Kawada

Iwamoto

et al. 2012

Intl Journal of Cancer

115

View full text Add to dashboard Cite

show abstract

“…Because the leading cause of deaths of patients with colon cancer is the metastatic dissemination and in particular the liver colonization, it is imperative to assess the therapeutic benefits of a new compound on experimental models of metastatic disease. The experiments we performed in a well-established model of colon dissemination disease, by intrasplenic injection of tumor cells (42,43), demonstrated that EMICORON treatment is able to inhibit the spreading of metastasis to both gastrointestinal organs and liver. The most recent class of preclinical models is PDXs, where tumor fragments from patients are directly implanted in immunodeficient mice and then passed directly from mouse to mouse in vivo.…”

Section: Discussionmentioning

confidence: 93%

Targeting G-Quadruplex DNA Structures by EMICORON Has a Strong Antitumor Efficacy against Advanced Models of Human Colon Cancer

Porru¹,

Artuso²,

Salvati³

et al. 2015

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

We previously identified EMICORON as a novel G-quadruplex (G4) ligand showing high selectivity for G4 structures over the duplex DNA, causing telomere damage and inhibition of cell proliferation in transformed and tumor cells. Here, we evaluated the antitumoral effect of EMICORON on advanced models of human colon cancer that could adequately predict human clinical outcomes. Our results showed that EMICORON was well tolerated in mice, as no adverse effects were reported, and a low ratio of sensitivity across human and mouse bone marrow cells was observed, indicating a good potential for reaching similar blood levels in humans. Moreover, EMICORON showed a marked therapeutic efficacy, as it inhibited the growth of patient-derived xenografts (PDX) and orthotopic colon cancer and strongly reduced the dissemination of tumor cells to lymph nodes, intestine, stomach, and liver. Finally, activation of DNA damage and impairment of proliferation and angiogenesis are proved to be key determinants of EMICORON antitumoral activity. Altogether, our results, performed on advanced experimental models of human colon cancer that bridge the translational gap between preclinical and clinical studies, demonstrated that EMICORON had an unprecedented antitumor activity warranting further studies of EMI-CORON-based combination treatments.

show abstract

“…LOX is one of the critical HIF-1 targets mediating tumor progression and catalyzes the cross-linking of collagens and elastin in the extracellular matrix, thereby regulating tissue tensile strength (Erler & Giaccia, 2006). Paradoxically, LOX has been reported to be both up-regulated and down-regulated in cancer cells, especially in colorectal cancer (Baker, 2011;Pez, 2011). Mechanistic investigations revealed that LOX activates the PI3K-Akt signaling pathway, thereby upregulating HIF-1 protein synthesis in a manner requiring LOX-mediated hydrogen peroxide production.…”

Section: Discussionmentioning

confidence: 99%

Molecular Portrait of Clear Cell Renal Cell Carcinoma: An Integrative Analysis of Gene Expression and Genomic Copy Number Profiling

Battaglia¹,

Mangano²,

Bicciato³

et al. 2012

Emerging Research and Treatments in Renal Cell Carcinoma

View full text Add to dashboard Cite

The Role of Lysyl Oxidase in SRC-Dependent Proliferation and Metastasis of Colorectal Cancer

Abstract: LOX showed an important role in CRC cell proliferation and metastasis and was dependent on the activation of SRC. These results have the potential to identify patients with high SRC activity, who may benefit from dasatinib treatment.

Cited by 177 publications

References 53 publications

The role of CXCR3 and CXCR4 in colorectal cancer metastasis

The role of CXCR3 and CXCR4 in colorectal cancer metastasis

Targeting G-Quadruplex DNA Structures by EMICORON Has a Strong Antitumor Efficacy against Advanced Models of Human Colon Cancer

Molecular Portrait of Clear Cell Renal Cell Carcinoma: An Integrative Analysis of Gene Expression and Genomic Copy Number Profiling

Contact Info

Product

Resources

About