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  Inhibition of fibronectin accumulation suppresses tumor growth

Ghura, H., Keimer, M., von Au, A., Hackl, N., Klemis, V., & Nakchbandi, I. A. (2021). Inhibition of fibronectin accumulation suppresses tumor growth. Neoplasia, 23(9), 837-850. doi:10.1016/j.neo.2021.06.012.

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Genre: Journal Article

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 Creators:
Ghura, Hiba1, Author
Keimer, Marin1, Author
von Au, Anja1, Author
Hackl, Norman1, Author
Klemis, Verena1, Author
Nakchbandi, Inaam A.2, Author              
Affiliations:
1external, ou_persistent22              
2Nakchbandi, Inaam / Translational Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565162              

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Free keywords: REGULATES CELL-PROLIFERATION; SIGNALING PATHWAY; MATRIX; ACTIVATION; PROMOTES; ANGIOGENESIS; APOPTOSIS; PROTEIN; ERK; LIGATIONOncology; Extracellular matrix; Fibronectin; Breast cancer; Melanoma; Pharmacologic matrix modulation; Collagen type I; pUR4; Functional upstream domain (FUD);
 Abstract: Understanding how the extracellular matrix affects cancer development constitutes an emerging research field. Fibronectin and collagen are two intriguing matrix components found in cancer. Large concentrations of fibronectin or collagen type I have been implicated in poor prognosis in patients. In a mouse model, we had shown that genetically decreasing circulating fibronectin resulted in smaller tumors. We therefore aimed to manipulate fibronectin pharmacologically and determine how cancer development is affected. Deletion of fibronectin in human breast cancer cells (MDA-MB-231) using shRNA (knockdown: Kd) improved survival and diminished tumor burden in a model of metastatic lesions and in a model of local growth. Based on these findings, it seemed reasonable to attempt to prevent fibronectin accumulation using a bacterial derived peptide called pUR4. Treatment with this peptide for 10 days in the breast cancer local growth model or for 5 days in a melanoma skin cancer model (B16) was associated with a significant suppression of cancer growth. Treatment aimed at inhibiting collagen type I accumulation without interfering with fibronectin could not affect any changes in vivo . In the absence of fibronectin, diminished cancer progression was due to inhibition of proliferation, even though changes in blood vessels were also detected. Decreased proliferation could be attributed to decreased ERK phosphorylation and diminished YAP expression. In summary, manipulating fibronectin diminishes cancer progression, mostly by suppressing cell proliferation. This suggests that matrix modulation could be used as an adjuvant to conventional therapy as long as a decrease in fibronectin is obtained.

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Language(s): eng - English
 Dates: 2021
 Publication Status: Published in print
 Pages: 14
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000691198900002
DOI: 10.1016/j.neo.2021.06.012
 Degree: -

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Title: Neoplasia
Source Genre: Journal
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Publ. Info: STE 800, 230 PARK AVE, NEW YORK, NY 10169 USA : ELSEVIER SCIENCE INC
Pages: - Volume / Issue: 23 (9) Sequence Number: - Start / End Page: 837 - 850 Identifier: ISSN: 1476-5586