Induction of epithelial‐mesenchymal transition with O‐glycosylated oncofetal fibronectin

Ding, Yao; Gelfenbeyn, Kirill; Freire-de-Lima, Leonardo; Handa, Kazuko; Hakomori, Sen‐itiroh

doi:10.1016/j.febslet.2012.05.020

Cited by 33 publications

(35 citation statements)

References 34 publications

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“…This opposite expression in primary and advanced tumors indicates a dual function at different stages of cancer. These miRNAs were found to be correlated with O-glycan biosynthesis; O-glycosylation has an important functional role in EMT induction (25,26). In line with these results, we found that genes that are positively correlated with P5 miRNAs are enriched by genes that are upregulated during EMT (ref.…”

Section: P1 Mirnas Differentiate Between Recurrence and Recurrencefresupporting

confidence: 82%

Tumor Evolution Inferred by Patterns of microRNA Expression through the Course of Disease, Therapy, and Recurrence in Breast Cancer

Dadiani

Ben-Moshe

Paluch‐Shimon

et al. 2016

Clinical Cancer Research

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Purpose: Molecular evolution of tumors during progression, therapy, and metastasis is a major clinical challenge and the main reason for resistance to therapy. We hypothesized that microRNAs (miRNAs) that exhibit similar variation of expression through the course of disease in several patients have a significant function in the tumorigenic process. Experimental design: Exploration of evolving disease by profiling 800 miRNA expression from serial samples of individual breast cancer patients at several time points: pretreatment, posttreatment, lymph nodes, and recurrence sites when available (58 unique samples from 19 patients). Using a dynamic approach for analysis, we identified expression modulation patterns and classified varying miRNAs into one of the eight possible temporal expression patterns. Results: The various patterns were found to be associated with different tumorigenic pathways. The dominant pattern identified an miRNA set that significantly differentiated between disease stages, and its pattern in each patient was also associated with response to therapy. These miRNAs were related to tumor proliferation and to the cell-cycle pathway, and their mRNA targets showed anticorrelated expression. Interestingly, the level of these miRNAs was lowest in matched recurrent samples from distant metastasis, indicating a gradual increase in proliferative potential through the course of disease. Finally, the average expression level of these miRNAs in the pretreatment biopsy was significantly different comparing patients experiencing recurrence to recurrence-free patients. Conclusions: Serial tumor sampling combined with analysis of temporal expression patterns enabled to pinpoint significant signatures characterizing breast cancer progression, associated with response to therapy and with risk of recurrence. Clin Cancer Res; 22(14); 3651–62. ©2016 AACR.

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Section: P1 Mirnas Differentiate Between Recurrence and Recurrencefresupporting

confidence: 82%

Tumor Evolution Inferred by Patterns of microRNA Expression through the Course of Disease, Therapy, and Recurrence in Breast Cancer

Dadiani

Ben-Moshe

Paluch‐Shimon

et al. 2016

Clinical Cancer Research

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“…A switch from E-cadherin to N-cadherin expression is of strong independent importance for the progress of prostate cancer [26][27][28][29] , and up-regulation of vimentin expression is linked to prostate cancer invasion [29] . Our findings add to the growing evidence linking glycosylation and the EMT transition [30][31][32][33] , and provide important insight into understanding how O-linked glycans can influence this process. Further dissection of the interplay between sTn and oncogenic features will require deciphering the effects of sTn on additional specific O-glycoproteins.…”

Section: Research Highlightsupporting

confidence: 61%

Sugars and cell adhesion: The role of ST6GalNAc1 in prostate cancer progression

Munkley

Elliott

2016

Cancer Cell Microenviron

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O-linked glycans become altered in cancer cells, leading to changes in cell adhesive properties and contributing to metastasis. But the mechanisms driving these changes and how these carbohydrate groups are involved in tumour spread remain poorly understood. We recently identified the sialyltransferase gene ST6GalNAc1 as a novel androgen-regulated gene in prostate cancer [1] . Expression of ST6GalNAc1 in prostate cancer cells induced expression of the cancer-associated sTn antigen, reduced cell adhesion, and dramatically inhibited the formation of stable tumour masses in vivo after orthotopic transplantation experiments in mice. Although ST6GalNAc1 is significantly upregulated in primary prostate carcinoma tissue, there is a striking downregulation of this gene in metastatic prostate tissue, suggesting an important yet transient role for ST6GalNAc1 in prostate cancer progression. Here we discuss mechanistically how changes in sialylation could alter prostate tumour cell behaviour and contribute to cancer cell dissemination.

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“…Cancer cells that undergo EMT upregulate FN along with other ECM molecules that constitute the remodeled ECM. Interestingly, secreted FN further stimulate EMT, for example, by sensitizing cancers to TGFβ induction, and trigger a variety of signaling pathways that in turn upregulate FN expression 14, 15 (Figure 2B). This feedback loop once again reflects a close alliance of FN and cancer cells.…”

Section: Upregulated Fibronectin Is a Cancer Markermentioning

confidence: 99%

Targeting fibronectin for cancer imaging and therapy

2017

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During cancer progression, the extracellular matrix (ECM) undergoes dramatic changes, which promote cancer cell migration and invasion. In the remodeled tumor ECM, fibronectin (FN) level is upregulated to assist tumor growth, progression, and invasion. FN serves as a central organizer of ECM molecules and mediates the crosstalk between the tumor microenvironment and cancer cells. Its upregulation is correlated with angiogenesis, cancer progression, metastasis, and drug resistance. A number of FN-targeting ligands have been developed for cancer imaging and therapy. Thus far, FN-targeting imaging agents have been tested for nuclear imaging, MRI, and fluorescence imaging, for tumor detection and localization. FN-targeting therapeutics, including nuclear medicine, chemotherapy drugs, cytokines, and photothermal moieties, were also developed in cancer therapy. Because of the prevalence of FN overexpression in cancer, FN targeting imaging agents and therapeutics have the promise of broad applications in the diagnosis, treatment, and image-guided interventions of many types of cancers. This review will summarize current understanding on the role of FN in cancer, discuss the design and development of FN-targeting agents, and highlight the applications of these FN-targeting agents in cancer imaging and therapy.

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Induction of epithelial‐mesenchymal transition with O‐glycosylated oncofetal fibronectin

Cited by 33 publications

References 34 publications

Tumor Evolution Inferred by Patterns of microRNA Expression through the Course of Disease, Therapy, and Recurrence in Breast Cancer

Tumor Evolution Inferred by Patterns of microRNA Expression through the Course of Disease, Therapy, and Recurrence in Breast Cancer

Sugars and cell adhesion: The role of ST6GalNAc1 in prostate cancer progression

Targeting fibronectin for cancer imaging and therapy

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