The Multifaceted Roles of EGFL7 in Cancer and Drug Resistance

SIMPLE SUMMARY: Cancer growth and metastasis require interactions with the extracellular matrix (ECM), which is home to many biomolecules that support the formation of new vessels and cancer growth. One of these biomolecules is epidermal growth factor-like protein-7 (EGFL7). EGFL7 alters cellular ad...

Descripción completa

Detalles Bibliográficos
Autores principales: Heissig, Beate, Salama, Yousef, Takahashi, Satoshi, Okumura, Ko, Hattori, Koichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957479/
https://www.ncbi.nlm.nih.gov/pubmed/33804387
http://dx.doi.org/10.3390/cancers13051014
_version_ 1783664657929601024
author Heissig, Beate
Salama, Yousef
Takahashi, Satoshi
Okumura, Ko
Hattori, Koichi
author_facet Heissig, Beate
Salama, Yousef
Takahashi, Satoshi
Okumura, Ko
Hattori, Koichi
author_sort Heissig, Beate
collection PubMed
description SIMPLE SUMMARY: Cancer growth and metastasis require interactions with the extracellular matrix (ECM), which is home to many biomolecules that support the formation of new vessels and cancer growth. One of these biomolecules is epidermal growth factor-like protein-7 (EGFL7). EGFL7 alters cellular adhesion to the ECM and migratory behavior of tumor and immune cells contributing to tumor metastasis. EGFL7 is engaged in the formation of new vessels and changes in ECM stiffness. One of its binding partners on the endothelial and cancer cell surface is beta 3 integrin. Beta 3 integrin pathways are under intense investigation in search of new therapies to kill cancer cells. All these properties enable EGFL7 to contribute to drug resistance. In this review, we give insight into recent studies on EGFL7 and its engagement with beta3 integrin, a marker predicting cancer stem cells and drug resistance. ABSTRACT: Invasion of cancer cells into surrounding tissue and the vasculature is an important step for tumor progression and the establishment of distant metastasis. The extracellular matrix (ECM) is home to many biomolecules that support new vessel formation and cancer growth. Endothelial cells release growth factors such as epidermal growth factor-like protein-7 (EGFL7), which contributes to the formation of the tumor vasculature. The signaling axis formed by EGFL7 and one of its receptors, beta 3 integrin, has emerged as a key mediator in the regulation of tumor metastasis and drug resistance. Here we summarize recent studies on the role of the ECM-linked angiocrine factor EGFL7 in primary tumor growth, neoangiogenesis, tumor metastasis by enhancing epithelial-mesenchymal transition, alterations in ECM rigidity, and drug resistance. We discuss its role in cellular adhesion and migration, vascular leakiness, and the anti-cancer response and provide background on its transcriptional regulation. Finally, we discuss its potential as a drug target as an anti-cancer strategy.
format Online
Article
Text
id pubmed-7957479
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-79574792021-03-16 The Multifaceted Roles of EGFL7 in Cancer and Drug Resistance Heissig, Beate Salama, Yousef Takahashi, Satoshi Okumura, Ko Hattori, Koichi Cancers (Basel) Review SIMPLE SUMMARY: Cancer growth and metastasis require interactions with the extracellular matrix (ECM), which is home to many biomolecules that support the formation of new vessels and cancer growth. One of these biomolecules is epidermal growth factor-like protein-7 (EGFL7). EGFL7 alters cellular adhesion to the ECM and migratory behavior of tumor and immune cells contributing to tumor metastasis. EGFL7 is engaged in the formation of new vessels and changes in ECM stiffness. One of its binding partners on the endothelial and cancer cell surface is beta 3 integrin. Beta 3 integrin pathways are under intense investigation in search of new therapies to kill cancer cells. All these properties enable EGFL7 to contribute to drug resistance. In this review, we give insight into recent studies on EGFL7 and its engagement with beta3 integrin, a marker predicting cancer stem cells and drug resistance. ABSTRACT: Invasion of cancer cells into surrounding tissue and the vasculature is an important step for tumor progression and the establishment of distant metastasis. The extracellular matrix (ECM) is home to many biomolecules that support new vessel formation and cancer growth. Endothelial cells release growth factors such as epidermal growth factor-like protein-7 (EGFL7), which contributes to the formation of the tumor vasculature. The signaling axis formed by EGFL7 and one of its receptors, beta 3 integrin, has emerged as a key mediator in the regulation of tumor metastasis and drug resistance. Here we summarize recent studies on the role of the ECM-linked angiocrine factor EGFL7 in primary tumor growth, neoangiogenesis, tumor metastasis by enhancing epithelial-mesenchymal transition, alterations in ECM rigidity, and drug resistance. We discuss its role in cellular adhesion and migration, vascular leakiness, and the anti-cancer response and provide background on its transcriptional regulation. Finally, we discuss its potential as a drug target as an anti-cancer strategy. MDPI 2021-03-01 /pmc/articles/PMC7957479/ /pubmed/33804387 http://dx.doi.org/10.3390/cancers13051014 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Heissig, Beate
Salama, Yousef
Takahashi, Satoshi
Okumura, Ko
Hattori, Koichi
The Multifaceted Roles of EGFL7 in Cancer and Drug Resistance
title The Multifaceted Roles of EGFL7 in Cancer and Drug Resistance
title_full The Multifaceted Roles of EGFL7 in Cancer and Drug Resistance
title_fullStr The Multifaceted Roles of EGFL7 in Cancer and Drug Resistance
title_full_unstemmed The Multifaceted Roles of EGFL7 in Cancer and Drug Resistance
title_short The Multifaceted Roles of EGFL7 in Cancer and Drug Resistance
title_sort multifaceted roles of egfl7 in cancer and drug resistance
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957479/
https://www.ncbi.nlm.nih.gov/pubmed/33804387
http://dx.doi.org/10.3390/cancers13051014
work_keys_str_mv AT heissigbeate themultifacetedrolesofegfl7incanceranddrugresistance
AT salamayousef themultifacetedrolesofegfl7incanceranddrugresistance
AT takahashisatoshi themultifacetedrolesofegfl7incanceranddrugresistance
AT okumurako themultifacetedrolesofegfl7incanceranddrugresistance
AT hattorikoichi themultifacetedrolesofegfl7incanceranddrugresistance
AT heissigbeate multifacetedrolesofegfl7incanceranddrugresistance
AT salamayousef multifacetedrolesofegfl7incanceranddrugresistance
AT takahashisatoshi multifacetedrolesofegfl7incanceranddrugresistance
AT okumurako multifacetedrolesofegfl7incanceranddrugresistance
AT hattorikoichi multifacetedrolesofegfl7incanceranddrugresistance