Matrix Metalloproteinases: A challenging paradigm of cancer management

Alaseem, Ali; Alhazzani, Khalid; Dondapati, Priya; Alobid, Saad; Bishayee, Anupam; Rathinavelu, Appu

doi:10.1016/j.semcancer.2017.11.008

Cited by 184 publications

(150 citation statements)

References 239 publications

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“…Besides, hypoxia-induced epithelial mesenchymal transition is an important mechanism of tumor progression, which is responsible for cancer cell migration and invasion [22,23]. MMPs, especially MMP9 and MMP2, are crucial biomarkers for migration and invasion in breast cancer [24][25][26]. By detecting MMPs levels and trans-well assay, we found that cell migration and invasion were increased in cells under hypoxia by increasing MMP2 and MMP9, which was inhibited by silence of circDENND4C.…”

Section: Discussionmentioning

confidence: 86%

Knockdown of circDENND4C inhibits glycolysis, migration and invasion by up-regulating miR-200b/c in breast cancer under hypoxia

Ren

Liu

Feng

et al. 2019

J Exp Clin Cancer Res

138

105

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Background: Hypoxia is a key feature of breast cancer, which affects cancer development, metastasis and metabolism. Previous studies suggested that circular RNAs (circRNAs) could participate in cancer progression and hypoxia regulation. This study aimed to investigate the role of circRNA differentially expressed in normal cells and neoplasia domain containing 4C (circDENND4C) in breast cancer progression under hypoxia. Methods: Forty-three patients with breast cancer were involved in this study. Breast cancer cell lines MDA-MB-453 and SK-BR-3 were cultured under hypoxia (1% O 2) for experiments in vitro. The expression levels of circDENND4C, microRNA-200b (miR-200b) and miR-200c were measured by quantitative real-time polymerase chain reaction. Glycolysis was investigated by glucose consumption, lactate production and hexokinase II (HK2) protein level. Migration and invasion were evaluated via trans-well assay and protein levels of matrix metallopeptidase 9 (MMP9) and MMP2. The interaction between circDENND4C and miR-200b or miR-200c was explored by bioinformatics analysis, luciferase assay and RNA immunoprecipitation. Murine xenograft model was established to investigate the anti-cancer role of circDENND4C in vivo. Results: circDENND4C highly expressed in breast cancer was up-regulated in response to hypoxia. Knockdown of circDENND4C decreased glycolysis, migration and invasion in breast cancer cells under hypoxia. circDENND4C was validated as a sponge of miR-200b and miR-200c. Deficiency of miR-200b or miR-200c reversed the suppressive effect of circDENND4C knockdown on breast cancer progression. Moreover, silence of circDENND4C reduced xenograft tumor growth by increasing miR-200b and miR-200c. Conclusion: circDENND4C silence suppresses glycolysis, migration and invasion in breast cancer cells under hypoxia by increasing miR-200b and miR-200c.

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Section: Discussionmentioning

confidence: 86%

Knockdown of circDENND4C inhibits glycolysis, migration and invasion by up-regulating miR-200b/c in breast cancer under hypoxia

Ren

Liu

Feng

et al. 2019

J Exp Clin Cancer Res

138

105

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“…The propeptide is crucial for MMP activation because it contains a "cysteine switch" motif in which cysteine binds to the Zn 2+ ion of the catalytic pocket. Once this linkage is cleaved, the catalytic pocket is accessible and the MMP becomes active (Tallant et al, 2010;Cui et al, 2017;Alaseem et al, 2019). For MMP2, this activation step occurs mainly at the plasma membrane and is mediated by membrane type 1 (MT1)-MMP, a membrane-bound protein of the same family that, in conjunction with tissue inhibitor of metalloproteinase 2 (TIMP2), cleaves the propeptide domain (Fernandez-Catalan et al, 1998;Brew and Nagase, 2010;Han et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Nucleobindin-1 regulates ECM degradation by promoting intra-Golgi trafficking of MMPs

Pacheco-Fernandez

Pakdel

Blank

et al. 2020

Journal of Cell Biology

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Matrix metalloproteinases (MMPs) degrade several ECM components and are crucial modulators of cell invasion and tissue organization. Although much has been reported about their function in remodeling ECM in health and disease, their trafficking across the Golgi apparatus remains poorly understood. Here we report that the cis-Golgi protein nucleobindin-1 (NUCB1) is critical for MMP2 and MT1-MMP trafficking along the Golgi apparatus. This process is Ca2+-dependent and is required for invasive MDA-MB-231 cell migration as well as for gelatin degradation in primary human macrophages. Our findings emphasize the importance of NUCB1 as an essential component of MMP transport and its overall impact on ECM remodeling.

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“…Although the decrease in the number of M2-like macrophages was only one quarter, both the number of CD8 + cells and the function of cytotoxic cells was significantly increased after the combined therapy (Figures 5c,d). [23] Furthermore, the expression of MMP9 protein and gene was significantly decreased in tumor tissues treated with PLG-CA4 and PI3Kγ inhibitor combination (Figure 5f). [22] Compared to PLG-CA4 alone, the CD31-positive signals were further reduced, and the intertumor microvessels were poorly structured after treatment with PI3Kγ inhibitor (Figure 5e).…”

Section: Mechanisms Of Antitumor Performance By Attenuating Immunosupmentioning

confidence: 94%

PI3Kgamma Inhibitor Attenuates Immunosuppressive Effect of Poly(l‐Glutamic Acid)‐Combretastatin A4 Conjugate in Metastatic Breast Cancer

Qin

Sheng

et al. 2019

Advanced Science

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Vascular disrupting agents (VDAs) have great potential for cancer treatment. Poly( l ‐glutamic acid)‐combretastatin A4 conjugate (PLG‐CA4) is a novel class of VDAs. Though it has notable antitumor activity, it can induce host immune responses that promote tumor growth. Here, PLG‐CA4 induces the polarization of tumor‐associated macrophages (TAMs) toward the M2‐like phenotype in 4T1 metastatic breast cancer (Control 30% vs PLG‐CA4 53%; p < 0.05). Compared to the monotherapy of PLG‐CA4, inhibition of phosphoinositide 3‐kinase gamma (PI3Kγ) attenuates the immunosuppressive effect of PLG‐CA4 treatment by decreasing the number of M2‐like TAMs (2.0 × 10 4 to 1.5 × 10 4 per tumor) and potential enhancement of cytotoxic T lymphocyte (3.0 × 10 4 to 5.7 × 10 4 per tumor). Importantly, PI3Kγ inhibitor synergizing with PLG‐CA4 significantly extends the mean survival time from 52 days in monotherapy‐treated mice to 61.8 days. Additionally, the combination of PLG‐CA4 and PI3Kγ inhibitor improves the tumor therapeutic effect of NLG919, an inhibitor of immune checkpoint indoleamine 2,3‐dioxygenase (IDO). As far as it is known, this is the first demonstrated study that VDAs induce the reshaping of macrophages to the M2‐like phenotype. The findings also indicate a potential therapeutic strategy of the combination VDAs with an accurate immune modifier in the tumor to reverse the immune resistance.

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Matrix Metalloproteinases: A challenging paradigm of cancer management

Cited by 184 publications

References 239 publications

Knockdown of circDENND4C inhibits glycolysis, migration and invasion by up-regulating miR-200b/c in breast cancer under hypoxia

Knockdown of circDENND4C inhibits glycolysis, migration and invasion by up-regulating miR-200b/c in breast cancer under hypoxia

Nucleobindin-1 regulates ECM degradation by promoting intra-Golgi trafficking of MMPs

PI3Kgamma Inhibitor Attenuates Immunosuppressive Effect of Poly(l‐Glutamic Acid)‐Combretastatin A4 Conjugate in Metastatic Breast Cancer

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