The Elastin Receptor Complex: A Unique Matricellular Receptor with High Anti-tumoral Potential

Abstract

Elastin, one of the longest-lived proteins, confers elasticity to tissues with high mechanical constraints. During aging or pathophysiological conditions such as cancer progression, this insoluble polymer of tropoelastin undergoes an important degradation leading to the release of bioactive elastin-derived peptides (EDPs), named elastokines. EDP exhibit several biological functions able to drive tumor development by regulating cell proliferation, invasion, survival, angiogenesis, and matrix metalloproteinase expression in various tumor and stromal cells. Although, several receptors have been suggested to bind elastokines (αvβ3 and αvβ5 integrins, galectin-3), their main receptor remains the elastin receptor complex (ERC). This heterotrimer comprises a peripheral subunit, named elastin binding protein (EBP), associated to the protective protein/cathepsin A (PPCA). The latter is bound to a membrane-associated protein called Neuraminidase-1 (Neu-1). The pro-tumoral effects of elastokines have been linked to their binding onto EBP. Additionally, Neu-1 sialidase activity is essential for their signal transduction. Consistently, EDP-EBP interaction and Neu-1 activity emerge as original anti-tumoral targets. Interestingly, besides its direct involvement in cancer progression, the ERC also regulates diabetes outcome and thrombosis, an important risk factor for cancer development and a vascular process highly increased in patients suffering from cancer. In this review, we will describe ERC and elastokines involvement in cancer development suggesting that this unique receptor would be a promising therapeutic target. We will also discuss the pharmacological concepts aiming at blocking its pro-tumoral activities. Finally, its emerging role in cancer-associated complications and pathologies such as diabetes and thrombotic events will be also considered.

Structural characterization andin vivopro-tumor properties of a highly conserved matrikine

“…Protease secretion by lung carcinoma cell lines could not be inhibited by lactose and V14, two ERC antagonists, or by blocking antibodies against αVβ3 integrin and galectin-3. Given these data, the implication of a single elastin receptor in tumor progression is no longer possible [ 47 ]. It is therefore important to consider the existence of a currently unknown or forgotten elastin receptor [ 39 ].…”

Characterization of Collagens Fibers (I, III, IV) and Elastin in the Extracellular Matrix of Normal and Neoplastic Canine Prostate

“…In canine PC, there was a tendency to higher median of elastin fibers, than normal tissue. Elastin fibers are involved in tumor invasion and metastasis [33], cell proliferation, adhesion, apoptosis and angiogenesis [34].…”

<p>Novel Molecular Mechanism of Aspirin and Celecoxib Targeting Mammalian Neuraminidase-1 Impedes Epidermal Growth Factor Receptor Signaling Axis and Induces Apoptosis in Pancreatic Cancer Cells</p>

“…Neu-1 activity has been reported to be associated with cell survival and proliferation. 49 We have reported on the role of mammalian Neu-1 in complex with MMP-9 and GPCRs tethered to RTKs and TLRs as a major target in multistage tumorigenesis. 31 Furthermore, we have reported on the efficacy of the combination of aspirin, metformin, and oseltamivir phosphate in sensitizing triple-negative breast cancer (TNBC) and its tamoxifen-resistant variant to tamoxifen in an additive therapeutic effect, reducing cell viability and cell proliferation and inducing early apoptosis and necrosis.…”