LymphedemaV1, Main, Exploration, bibRecord, 001F59

Constitutive Activation of mTORC1 in Endothelial Cells Leads to the Development and Progression of Lymphangiosarcoma through VEGF Autocrine Signaling

Identifieur interne : 001F59 ( Main/Exploration ); précédent : 001F58; suivant : 001F60

Constitutive Activation of mTORC1 in Endothelial Cells Leads to the Development and Progression of Lymphangiosarcoma through VEGF Autocrine Signaling

Auteurs : Shaogang Sun [États-Unis] ; Song Chen [États-Unis] ; Fei Liu [États-Unis] ; Haige Wu [États-Unis] ; Jonathan Mchugh [États-Unis] ; Ingrid L. Bergin [États-Unis] ; Anita Gupta [États-Unis] ; Denise Adams [États-Unis] ; Jun-Lin Guan [États-Unis]

Source :

Cancer cell [ 1535-6108 ] ; 2015.

RBID : PMC:4828306

Abstract

Summary

Angiosarcoma/lymphangiosarcoma is a rare malignancy with poor prognosis. We generated a mouse model with inducible endothelial cell-specific deletion of Tsc1 to examine mTORC1 signaling in lymphangiosarcoma. Tsc1 loss increased retinal angiogenesis in neonates, and led to endothelial proliferative lesions from vascular malformations to vascular tumors in adult mice. Sustained mTORC1 signaling was required for lymphangiosarcoma development and maintenance. Increased VEGF expression in tumor cells was seen, and blocking autocrine VEGF signaling abolished vascular tumor development and growth. We also found significant correlations between mTORC1 activation and VEGF, HIF1α, and c-Myc expression in human angiosarcoma samples. These studies demonstrated critical mechanisms of aberrant mTORC1 activation in lymphangiosarcoma, and validate the mice as a valuable model for further study.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4828306

DOI: 10.1016/j.ccell.2015.10.004
PubMed: 26777415
PubMed Central: 4828306

Affiliations:

Le document en format XML

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<p id="P1">Angiosarcoma/lymphangiosarcoma is a rare malignancy with poor prognosis. We generated a mouse model with inducible endothelial cell-specific deletion of <italic>Tsc1</italic>
 to examine mTORC1 signaling in lymphangiosarcoma. <italic>Tsc1</italic>
 loss increased retinal angiogenesis in neonates, and led to endothelial proliferative lesions from vascular malformations to vascular tumors in adult mice. Sustained mTORC1 signaling was required for lymphangiosarcoma development and maintenance. Increased VEGF expression in tumor cells was seen, and blocking autocrine VEGF signaling abolished vascular tumor development and growth. We also found significant correlations between mTORC1 activation and VEGF, HIF1α, and c-Myc expression in human angiosarcoma samples. These studies demonstrated critical mechanisms of aberrant mTORC1 activation in lymphangiosarcoma, and validate the mice as a valuable model for further study.</p>
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Serveur d'exploration sur le lymphœdème

Constitutive Activation of mTORC1 in Endothelial Cells Leads to the Development and Progression of Lymphangiosarcoma through VEGF Autocrine Signaling

Constitutive Activation of mTORC1 in Endothelial Cells Leads to the Development and Progression of Lymphangiosarcoma through VEGF Autocrine Signaling

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Abstract

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