The Biochemistry and Physiology of A Disintegrin and Metalloproteinases (ADAMs and ADAM-TSs) in Human Pathologies

Sharma, Deepti; Singh, Nikhlesh K.

doi:10.1007/112_2021_67

Cited by 5 publications

(3 citation statements)

References 260 publications

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“…As shown in Figure 2, ADAM17 can be phosphorylated by various protein kinases, such as PKC (3), PKL2 (3), PTK2 (18), MAPKs (3,62), Akt/GSK (63), and Smad2/3 (64). Recent studies have shown that the extracellular domain of ADAM17 with a homodimer structure can bind tightly to selective ADAM17 inhibitors, while serine 819 (Ser 819 ) and threonine 735 (Thr 735 ) in the cytoplasmic tail release selective ADAM17 inhibitors, which activate ADAM17 by inhibiting its phosphorylation-induced dimerization (65,66). In addition, ADAM17 phosphorylation further promotes the shedding of TNF-a and two TNF receptors (32).…”

Section: Regulatory Roles Of Adam17 Adam17 Regulates Post-translation...mentioning

confidence: 99%

Immunomodulatory role of metalloproteinase ADAM17 in tumor development

et al. 2022

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ADAM17 is a member of the a disintegrin and metalloproteinase (ADAM) family of transmembrane proteases involved in the shedding of some cell membrane proteins and regulating various signaling pathways. More than 90 substrates are regulated by ADAM17, some of which are closely relevant to tumor formation and development. Besides, ADAM17 is also responsible for immune regulation and its substrate-mediated signal transduction. Recently, ADAM17 has been considered as a major target for the treatment of tumors and yet its immunomodulatory roles and mechanisms remain unclear. In this paper, we summarized the recent understanding of structure and several regulatory roles of ADAM17. Importantly, we highlighted the immunomodulatory roles of ADAM17 in tumor development, as well as small molecule inhibitors and monoclonal antibodies targeting ADAM17.

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Section: Regulatory Roles Of Adam17 Adam17 Regulates Post-translation...mentioning

confidence: 99%

Immunomodulatory role of metalloproteinase ADAM17 in tumor development

et al. 2022

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“…Like MMPs, ADAMs are often upregulated in tumors and high levels associate with a worse prognosis for the patients ( 136 – 141 ). Only recently, ADAMs have been linked to the immune cell infiltration and immune checkpoint molecule expression.…”

Section: Resultsmentioning

confidence: 99%

The entanglement of extracellular matrix molecules and immune checkpoint inhibitors in cancer: a systematic review of the literature

Fejza,

Carobolante,

Poletto

et al. 2023

Front. Immunol.

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IntroductionImmune-checkpoint inhibitors (ICIs) have emerged as a core pillar of cancer therapy as single agents or in combination regimens both in adults and children. Unfortunately, ICIs provide a long-lasting therapeutic effect in only one third of the patients. Thus, the search for predictive biomarkers of responsiveness to ICIs remains an urgent clinical need. The efficacy of ICIs treatments is strongly affected not only by the specific characteristics of cancer cells and the levels of immune checkpoint ligands, but also by other components of the tumor microenvironment, among which the extracellular matrix (ECM) is emerging as key player. With the aim to comprehensively describe the relation between ECM and ICIs’ efficacy in cancer patients, the present review systematically evaluated the current literature regarding ECM remodeling in association with immunotherapeutic approaches.MethodsThis review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and was registered at the International Prospective Register of Systematic Reviews (PROSPERO, CRD42022351180). PubMed, Web of Science, and Scopus databases were comprehensively searched from inception to January 2023. Titles, abstracts and full text screening was performed to exclude non eligible articles. The risk of bias was assessed using the QUADAS-2 tool.ResultsAfter employing relevant MeSH and key terms, we identified a total of 5070 studies. Among them, 2540 duplicates, 1521 reviews or commentaries were found and excluded. Following title and abstract screening, the full text was analyzed, and 47 studies meeting the eligibility criteria were retained. The studies included in this systematic review comprehensively recapitulate the latest observations associating changes of the ECM composition following remodeling with the traits of the tumor immune cell infiltration. The present study provides for the first time a broad view of the tight association between ECM molecules and ICIs efficacy in different tumor types, highlighting the importance of ECM-derived proteolytic products as promising liquid biopsy-based biomarkers to predict the efficacy of ICIs.ConclusionECM remodeling has an important impact on the immune traits of different tumor types. Increasing evidence pinpoint at ECM-derived molecules as putative biomarkers to identify the patients that would most likely benefit from ICIs treatments.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022351180, identifier CRD42022351180.

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“…The adamalysin family consists of disintegrin and metalloproteinases (ADAMs) as well as disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) subgroups [101]. Over the years, however, MMPs have been found to regulate pathways involved in apoptosis, immunity, cellular migration, wound healing, and tissue repair, as well as angiogenesis [102].…”

Section: Mmps In Ecm Remodeling and Pc Metastatic Progression: The An...mentioning

confidence: 99%

The Androgen Regulation of Matrix Metalloproteases in Prostate Cancer and Its Related Tumor Microenvironment

et al. 2023

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Prostate cancer represents the most common type of cancer among males and the second leading cause of cancer death in men in Western society. In most cases (~70%), PC has a slow and symptom-free growth, whereas it is more aggressive in the remaining patients. Current PC therapies prevalently target the proliferative function of the androgen receptor and may only be effective within short periods, beyond which the disease will progress to metastatic and castration-resistant phenotype. Preclinical and clinical studies are aimed at investigating the molecular basis for prostate cancer spreading. Although considerable efforts have been made to dissect the programs that foster prostate cancer spreading, few biomarkers predictive of metastatic phenotype have yet been identified and few therapeutic options are available for treatment of the metastatic disease. In the present paper, we will discuss innovative aspects of prostate cancer biology, which impinge on the role of cancer-associated fibroblasts and the released matrix metalloproteinases in the disease progression. Investigating these aspects might allow the discovery of clinically actionable biomarkers to target in the advanced stages of prostate cancer.

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The Biochemistry and Physiology of A Disintegrin and Metalloproteinases (ADAMs and ADAM-TSs) in Human Pathologies

Cited by 5 publications

References 260 publications

Immunomodulatory role of metalloproteinase ADAM17 in tumor development

Immunomodulatory role of metalloproteinase ADAM17 in tumor development

The entanglement of extracellular matrix molecules and immune checkpoint inhibitors in cancer: a systematic review of the literature

The Androgen Regulation of Matrix Metalloproteases in Prostate Cancer and Its Related Tumor Microenvironment

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