A Novel CD44-binding Peptide from the Pro-Matrix Metalloproteinase-9 Hemopexin Domain Impairs Adhesion and Migration of Chronic Lymphocytic Leukemia (CLL) Cells

Ugarte-Berzal, Estefanía; Bailón, Elvira; Amigo-Jiménez, Irene; Albar, Juan Pablo; García-Marco, José A.; García-Pardo, Ángeles

doi:10.1074/jbc.m114.559187

Cited by 31 publications

(36 citation statements)

References 32 publications

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“…Sequence-alignment studies of human MMP9 revealed that its PEX9 domain shows low homology with other MMP PEX domains (25%-30% amino acid identity), thereby suggesting PEX9 as a potential therapeutic target for selective MMP9 inhibition. 114,115 Ugarte-Berzal et al also have shown that although MMP9 degrades gelatin, the PEX9 domain inhibits this degradation by shielding gelatin and averting its interaction with the MMP9 catalytic site. 114,115 The PEX9 domain may regulate intracellular signaling and survival in chronic lymphocytic leukemia (CLL) cells.…”

Section: Mmps As Signaling Molecules Noncatalytic Functionsmentioning

confidence: 99%

“…114,115 Ugarte-Berzal et al also have shown that although MMP9 degrades gelatin, the PEX9 domain inhibits this degradation by shielding gelatin and averting its interaction with the MMP9 catalytic site. 114,115 The PEX9 domain may regulate intracellular signaling and survival in chronic lymphocytic leukemia (CLL) cells. 114,115 Ugarte-Berzal et al reported that the PEX9 domain contributes to CLL progression, and found a connection between blade B4 and the α 4 β 1 integrin.…”

Section: Mmps As Signaling Molecules Noncatalytic Functionsmentioning

confidence: 99%

“…114,115 Ugarte-Berzal et al reported that the PEX9 domain contributes to CLL progression, and found a connection between blade B4 and the α 4 β 1 integrin. 114,115 These authors recently proposed a novel PEX9 sequence involved in CLL PEX9-pro-MMP9 binding and interaction with CD44. 115 In other relevant studies, pro-MMP9 was shown to bind with the Ku protein through its PEX domain to promote the migration of acute myeloid leukemia cells, 116 whereas PEX9 and CD44 interaction in COS1 monkey kidney cells induced cell migration.…”

Section: Mmps As Signaling Molecules Noncatalytic Functionsmentioning

confidence: 99%

“…114,115 These authors recently proposed a novel PEX9 sequence involved in CLL PEX9-pro-MMP9 binding and interaction with CD44. 115 In other relevant studies, pro-MMP9 was shown to bind with the Ku protein through its PEX domain to promote the migration of acute myeloid leukemia cells, 116 whereas PEX9 and CD44 interaction in COS1 monkey kidney cells induced cell migration. 117 Furthermore, thrombin-mediated invasion of U2 osteosarcoma cells involved a PEX9 and β 1 -integrin association, 118 while MMP9 catalytic and PEX domains have been reported to induce FGF2-mediated angiogenesis in neutrophils.…”

Section: Mmps As Signaling Molecules Noncatalytic Functionsmentioning

confidence: 99%

“…114,115 The PEX9 domain may regulate intracellular signaling and survival in chronic lymphocytic leukemia (CLL) cells. 114,115 Ugarte-Berzal et al reported that the PEX9 domain contributes to CLL progression, and found a connection between blade B4 and the α 4 β 1 integrin. 114,115 These authors recently proposed a novel PEX9 sequence involved in CLL PEX9-pro-MMP9 binding and interaction with CD44.…”

Section: Mmps As Signaling Molecules Noncatalytic Functionsmentioning

confidence: 99%

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Matrix metalloproteinases in head and neck cancer: current perspectives

Gkouveris¹,

Nikitakis²,

Aseervatham³

et al. 2017

MNM

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Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases encoded by 24 distinct genes. Their functions have been implicated in numerous normal and pathologic processes, including uterine involution and organogenesis, inflammation and wound healing, vascular and autoimmune disease progression. Pertinent to this review, the role of MMPs in cancer biology is fairly well researched and documented, and remains a subject of continuing intense investigation. Not only are several MMPs overexpressed in head and neck squamous cell carcinomas (HNSCCs), expression has been correlated with salient tumorigenic hallmarks, such as cell proliferation, angiogenesis, invasion, and metastasis. The utility of changes in the expression profile, as well as various MMP polymorphisms as potential prognostic markers in oral cancers and oral premalignant lesions, have been investigated. Furthermore, the potential therapeutic utility of targeting MMPs in cancer remains attractive, although outcomes in this respect appear so far to be less encouraging with respect to HNSCCs. Because of the disappointing results observed in clinical trials where MMP-targeting regimens for HNSCCs utilized broad-spectrum small MMP catalytic site inhibitors, investigators now envision new strategies for MMP-specific targeting based on the recognition of new noncatalytic MMP domains with distinct functions. This review provides an overview of MMP activities in general and in cancers, and an update of their activities in HNSCC. Specifically, their role in the development and progression of HNSCC and their function as signaling molecules is discussed. Finally, their role as potential prognostic biomarkers and therapeutic targets in HNSCC is revisited.

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Section: Mmps As Signaling Molecules Noncatalytic Functionsmentioning

confidence: 99%

Section: Mmps As Signaling Molecules Noncatalytic Functionsmentioning

confidence: 99%

Section: Mmps As Signaling Molecules Noncatalytic Functionsmentioning

confidence: 99%

Section: Mmps As Signaling Molecules Noncatalytic Functionsmentioning

confidence: 99%

Section: Mmps As Signaling Molecules Noncatalytic Functionsmentioning

confidence: 99%

See 3 more Smart Citations

Matrix metalloproteinases in head and neck cancer: current perspectives

Gkouveris¹,

Nikitakis²,

Aseervatham³

et al. 2017

MNM

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Exploiting Hyaluronan-CD44 Network in Tumor Therapy

Karalis

Skandalis²

2022

The Extracellular Matrix and the Tumor Microenvironment

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Perspectives of CD44 targeting therapies

Orian-Rousseau

Ponta

2014

Arch Toxicol

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CD44 is a family of single-span transmembrane glycoproteins. Members of this family differ in the extracellular domain where ten variant exons are either excluded or included in various combinations. CD44 isoforms participate in many physiological processes including hematopoiesis, regeneration, lymphocyte homing and inflammation. Most importantly, they are involved in pathological processes and in particular in cancer. In several types of tumors, CD44 together with other antigens specifies for cancer stem cell populations. Mechanistically, CD44 proteins act as receptors for hyaluronan, co-receptor for receptor tyrosine kinases (RTKs) or G-protein-coupled receptors or provide a platform for metalloproteinases. For all these reasons, targeting CD44 may be a successful approach in cancer therapy. In this review, we discuss the various possibilities of targeting CD44. Among these are the production of CD44 ectodomains, antibodies, peptides or aptamers. Also inhibition of CD44 expression has been proposed. Finally, the function of CD44 as a hyaluronan receptor was also taken advantage of. We are convinced that the success of these therapies will depend on an increased understanding of the molecular functions of specific CD44 isoforms in particular in cancer stem cells.

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A Novel CD44-binding Peptide from the Pro-Matrix Metalloproteinase-9 Hemopexin Domain Impairs Adhesion and Migration of Chronic Lymphocytic Leukemia (CLL) Cells

Cited by 31 publications

References 32 publications

Matrix metalloproteinases in head and neck cancer: current perspectives

Matrix metalloproteinases in head and neck cancer: current perspectives

Exploiting Hyaluronan-CD44 Network in Tumor Therapy

Perspectives of CD44 targeting therapies

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