Role of Matrix Metalloproteinases in Angiogenesis and Cancer

Quintero-Fabián, Saray; Arreola, Rodrigo; Becerril-Villanueva, Enrique; Torres‐Romero, Julio César; Arana-Argáez, Víctor; Lara-Riegos, Julio; Ramírez-Camacho, Mario Alberto; Álvarez-Sánchez, María Elizbeth

doi:10.3389/fonc.2019.01370

Cited by 620 publications

(478 citation statements)

References 200 publications

(157 reference statements)

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“…Regardless of the timing of angiogenesis, the first step before growth factors recruitment and epithelial cells proliferation is the degradation of the epithelial layer of the existing vessel operated by the matrix metalloproteinases (MMPs) [26]. The latter play a role in the activation of the pro-angiogenic factors, exerting an important cross-talk with VEGF both in normal and pathological angiogenesis [27,28].…”

Section: Introductionmentioning

confidence: 99%

Uncovering the Physiological Mechanisms Underlying the Roe Deer (Capreolus capreolus) Testicular Cycle: Analyses of Gelatinases and VEGF Patterns and Correlation with Testes Weight and Testosterone

Elmi

Zannoni

Govoni

et al. 2020

Animals

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The roe deer (Capreolus capreolus) represents a spontaneous model of testicular inactivation: During winter, bucks show a suspension of spermatogenesis that starts again in spring and peaks during the breeding season (July–August). The underlying mechanisms to the regulation of the cyclic testicular changes are still not fully clear but seem to be imputable to the spermatogenic cell line since other testicular cell populations remain stable without apoptotic phenomena. The aim of the study was to investigate apoptosis, gelatinases (MMP2 and 9), their inhibiting factors (TIMP 1-2), and two isoforms of vascular endothelial growth factor (VEGF121 and 165) with its receptors (VEGFR1-2) in testes collected during pre- and post-rut periods, and to correlate them with testicular weight (TW) and testosterone (TEST). Testes from 18 adult sexually mature bucks were collected in Bologna Apennines (Italy). Samples were weighed and parenchyma collected. Radioimmunoassay, real-time PCR, and zymography were performed. The results showed a post-rut decrease in TW and TEST and an increase in proMMP2, also highlighting a correlation between the gelatinases and the testicular functionality. The VEGF pattern did not show modifications nor correlation with TW and TEST. Overall, gelatinases and their inhibitors, described herein for the first time in roe deer testes, seem to play an important role in the testicular cycle.

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Section: Introductionmentioning

confidence: 99%

Uncovering the Physiological Mechanisms Underlying the Roe Deer (Capreolus capreolus) Testicular Cycle: Analyses of Gelatinases and VEGF Patterns and Correlation with Testes Weight and Testosterone

Elmi

Zannoni

Govoni

et al. 2020

Animals

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“…SiRNA-mediated knockdown of PKM2 resulted in an upregulation of tumor suppressors, including Bad, caspase 7, and E-cadherin, whereas oncogenes, such as MMP-2, MMP-9, HIF1α, and VEGF, were downregulated in the SK-OV-3 cells [15]. MMP-2 and MMP-9, which belong to the MMP family, are closely associated with the metastasis of tumor cells [29,30].…”

Section: Discussionmentioning

confidence: 99%

Compound 3K, a Specific Pyruvate Kinase M2 Inhibitor, Induces Autophagic Cell Death through the Disruption of the Glycolytic Pathway in Ovarian Cancer Cells

Park¹,

Kundu²,

Kim³

et al. 2020

Preprint

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Ovarian cancer is the common cause of death among gynecological cancers. Although ovarian cancer initially responds to chemotherapy, the frequent recurrence in patients remains a therapeutic challenge. Pyruvate kinase M2 (PKM2) plays a pivotal role in regulating cancer cell survival. However, its therapeutic roles remain unclear. Here, we investigated the anticancer effects of compound 3K, a specific PKM2 inhibitor, on autophagic and apoptotic pathway regulation in SK-OV-3 (PKM2-overexpressing human ovarian adenocarcinoma cell line). The anticancer effect of compound 3K was examined using the MTT and colony formation assay in SK-OV-3. The results of tissue microarray showed that PKM2 expression positively correlated with the severity of the tumor. Moreover, the expression of pro-apoptotic proteins increased in SK-OV-3 following compound 3K treatment. Compound 3K induced AMPK activation, which was accompanied by the inhibition of mTOR. Additionally, this compound inhibited glycolysis, resulting in reduced proliferation in SK-OV-3. Compound 3K treatment suppressed tumor progression in vivo xenograft model. Our findings suggest that the inhibition of PKM2 by compound 3K affected Warburg effects and induced autophagic cell death. Therefore, the use of specific PKM2 inhibitors to block the glycolytic pathway and target cancer cell metabolism represents a promising therapeutic approach for treating PKM2-overexpressing ovarian cancer.

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“…A panel of five genes (CXCL12, IGF1, LEF1, MMP1, and RACGAP1) was proposed as biomarkers for prognosis through the survival analysis of BRCA [ 27 ]. MMPs are rather considered as target genes of EMT pathways and MMP expression as a late event of the EMT, being interconnected with key transcription factors, such as Snail, ETS, and β-catenin [ 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

Cancer-Associated Stemness and Epithelial-to-Mesenchymal Transition Signatures Related to Breast Invasive Carcinoma Prognostic

Groza

Braicu

Jurj

et al. 2020

Cancers

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Breast cancer is one of the most common oncological diseases in women, as its incidence is rapidly growing, rendering it unpredictable and causing more harm than ever before on an annual basis. Alterations of coding and noncoding genes are related to tumorigenesis and breast cancer progression. In this study, several key genes associated with epithelial-to-mesenchymal transition (EMT) and cancer stem cell (CSC) features were identified. EMT and CSCs are two key mechanisms responsible for self-renewal, differentiation, and self-protection, thus contributing to drug resistance. Therefore, understanding of the relationship between these processes may identify a therapeutic vulnerability that can be further exploited in clinical practice, and evaluate its correlation with overall survival rate. To determine expression levels of altered coding and noncoding genes, The Cancer Omics Atlas (TCOA) are used, and these data are overlapped with a list of CSCs and EMT-specific genes downloaded from NCBI. As a result, it is observed that CSCs are reciprocally related to EMT, thus identifying common signatures that allow for predicting the overall survival for breast cancer genes (BRCA). In fact, common CSCs and EMT signatures, represented by ALDH1A1, SFRP1, miR-139, miR-21, and miR-200c, are deemed useful as prognostic biomarkers for BRCA. Therefore, by mapping changes in gene expression across CSCs and EMT, suggesting a cross-talk between these two processes, we have been able to identify either the most common or specific genes or miRNA markers associated with overall survival rate. Thus, a better understanding of these mechanisms will lead to more effective treatment options.

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Role of Matrix Metalloproteinases in Angiogenesis and Cancer

Cited by 620 publications

References 200 publications

Uncovering the Physiological Mechanisms Underlying the Roe Deer (Capreolus capreolus) Testicular Cycle: Analyses of Gelatinases and VEGF Patterns and Correlation with Testes Weight and Testosterone

Uncovering the Physiological Mechanisms Underlying the Roe Deer (Capreolus capreolus) Testicular Cycle: Analyses of Gelatinases and VEGF Patterns and Correlation with Testes Weight and Testosterone

Compound 3K, a Specific Pyruvate Kinase M2 Inhibitor, Induces Autophagic Cell Death through the Disruption of the Glycolytic Pathway in Ovarian Cancer Cells

Cancer-Associated Stemness and Epithelial-to-Mesenchymal Transition Signatures Related to Breast Invasive Carcinoma Prognostic

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