Pericellular proteolysis in cancer

Sevenich, Lisa; Joyce, Johanna A.

doi:10.1101/gad.250647.114

Cited by 160 publications

(136 citation statements)

References 211 publications

(206 reference statements)

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“…Matrix metalloproteinases (MMPs) are members of pericellular proteases that are able to degrade proteolytic extracellular matrix (ECM) components (6). Despite abundant evidence showing that overexpression of MMPs correlates with tumor aggressiveness and metastatic potential in various cancers such as ovarian, lung, prostate, breast and pancreatic, the role of nicotine in this scenario is not fully understood.…”

Section: Discussionmentioning

confidence: 99%

“…Invasive migration and proteolytic extracellular matrix (ECM) remodelling are believed to be independent processes that control cancer cell invasion (5). Matrix metalloproteinases (MMPs) are members of pericellular proteases that are able to degrade ECM components (6). Upregulation of MMP-2 and MMP-9 was reported to accelerate cell migration and invasion in CRC (7).…”

Section: Introductionmentioning

confidence: 99%

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Nicotine enhances invasion and metastasis of human colorectal cancer cells through the nicotinic acetylcholine receptor downstream p38 MAPK signaling pathway

et al. 2015

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Abstract. Nicotine as a cigarette component is an established risk factor for colorectal cancer tumorigenesis. The downstream signaling pathways of nicotinic acetylcholine receptors (nAchRs) are believed to be responsible for the cellular effects. In the present study, we evaluated the effects and novel mechanisms for nicotine on the capacity for colorectal cancer cell invasion and metastasis. LOVO and SW620 colorectal cancer cells were stimulated with nicotine in vitro. A Transwell chamber model was applied to detect the capacity for tumor cell invasion. Assays for gelatin zymography and western blotting were applied to detect the activity and expression of metastasis-related matrix metalloproteinases (MMPs), respectively. Signal transduction was assessed by immunoblotting for the phosphorylation of relevant signal molecules and the application of pharmaceutical inhibitors. We showed that nicotine increased LOVO and SW620 colorectal cancer cell invasion along with enhanced activity and expression of MMP-1, -2 and -9. Nicotine increased phosphorylation of p38, ERK, Akt and PI3K p85 but had no effect on phosphorylation of JNK, or NF-κB. Of the pharmaceutical inhibitors of U0126 (ERK1/2 inhibitor), LY294002 (Akt activation inhibitor), SB239063 (p38 MAPK activation inhibitor) and hexamethonium (Hex) (nAchRs inhibitor), the cellular and molecular effects were reduced by the applications of SB239063 and Hex. We concluded that nicotine stimulates the invasion and metastasis of colon cancer cells in vitro via activation of the nAchRs and the p38 MAPK downstream signaling pathway. Therefore, p38 MAPK may have potential as a therapeutic target for smoking-related human colorectal cancer metastasis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nicotine enhances invasion and metastasis of human colorectal cancer cells through the nicotinic acetylcholine receptor downstream p38 MAPK signaling pathway

et al. 2015

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“…Received July 26, 2014;revised version accepted August 29, 2014. Tumors arise in complex tissue microenvironments in which a multitude of different noncancerous cell types can potently regulate disease initiation and progression (Hanahan and Coussens 2012;Quail and Joyce 2013). In addition, interactions with the extracellular matrix (ECM) are critical for modulating cell behavior, including enhancing cell survival and promoting invasion via ECM turnover and proteolysis (Lu et al 2012;Sevenich and Joyce 2014). The ECM is a heterogeneous mix of proteins and polysaccharides, including different collagens, laminins, fibronectin, and heparan sulfate proteoglycans, which form an intricate network that confers tissue structure and regulates growth factor availability (Hynes and Naba 2012;Lu et al 2012).…”

mentioning

confidence: 99%

Distinct functions of macrophage-derived and cancer cell-derived cathepsin Z combine to promote tumor malignancy via interactions with the extracellular matrix

et al. 2014

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During the process of tumor progression, cancer cells can produce the requisite growth-and invasion-promoting factors and can also rely on noncancerous cells in the tumor microenvironment as an alternative, cell-extrinsic source. However, whether the cellular source influences the function of such tumor-promoting factors remains an open question. Here, we examined the roles of the cathepsin Z (CtsZ) protease, which is provided by both cancer cells and macrophages in pancreatic neuroendocrine tumors in humans and mice. We found that tumor proliferation was exclusively regulated by cancer cell-intrinsic functions of CtsZ, whereas tumor invasion required contributions from both macrophages and cancer cells. Interestingly, several of the tumor-promoting functions of CtsZ were not dependent on its described catalytic activity but instead were mediated via the Arg-Gly-Asp (RGD) motif in the enzyme prodomain, which regulated interactions with integrins and the extracellular matrix. Together, these results underscore the complexity of interactions within the tumor microenvironment and indicate that cellular source can indeed impact molecular function.[Keywords: cell invasion; cell migration; tumor microenvironment; protease] Supplemental material is available for this article. Received July 26, 2014; revised version accepted August 29, 2014. Tumors arise in complex tissue microenvironments in which a multitude of different noncancerous cell types can potently regulate disease initiation and progression (Hanahan and Coussens 2012;Quail and Joyce 2013). In addition, interactions with the extracellular matrix (ECM) are critical for modulating cell behavior, including enhancing cell survival and promoting invasion via ECM turnover and proteolysis (Lu et al. 2012;Sevenich and Joyce 2014). The ECM is a heterogeneous mix of proteins and polysaccharides, including different collagens, laminins, fibronectin, and heparan sulfate proteoglycans, which form an intricate network that confers tissue structure and regulates growth factor availability (Hynes and Naba 2012;Lu et al. 2012). Integrins are central in mediating interactions between cells and the surrounding ECM, and integrin engagement at the cell surface results in activation of downstream signaling nodes, including focal adhesion kinase (FAK) and Src kinase, to promote cancer cell proliferation, survival, migration, and invasion (Desgrosellier and Cheresh 2010;Huttenlocher and Horwitz 2011;Moreno-Layseca and Streuli 2014).Among the noncancerous cell types that modulate tumorigenesis, tumor-associated macrophages (TAMs) have emerged as critical regulators of tumor progression (Biswas et al. 2013;Noy and Pollard 2014). This is particularly evident in tumor invasion, as TAMs provide a major source of proteases that modulate the ECM (Joyce and Pollard 2009). In determining the mechanisms by which TAMs promote different tumorigenic processes, the focus to date has been predominantly centered on identifying factors that are TAM-specific or TAM-enriched, which are not necessa...

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“…Proinflammatory cytokines stimulate expression, secretion and activation of MMPs in cancer cells, as well as in various stromal cell types (Sevenich and Joyce, 2014). Stromal cells secrete cytokines, which induce the expression of MMPs in cancer cells and thus promote their invasion, as was illustrated by Kenig et al (2010) in an in vitro glioma and endothelial cell co-culture.…”

Section: Cytokine Signalling Affects Protease Activitymentioning

confidence: 99%

“…Cytokines can act in autocrine or paracrine manners to exert their functions such as regulating cell proliferation in the TME. Additionally, cytokines enhance cancer cell invasion and tumour angiogenesis by inducing the expression of invasion-associated proteolytic enzymes (Kenig et al, 2010;Sevenich and Joyce, 2014) as is discussed in the next chapter.…”

Section: Protease Signalling: Cytokines As Protease Substratesmentioning

confidence: 99%

Proteases and cytokines as mediators of interactions between cancer and stromal cells in tumours

Breznik

Motaln

Turnšek

2017

Biological Chemistry

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Proteolytic enzymes are highly relevant in different processes of cancer progression. Their interplay with other signalling molecules such as cytokines represents important regulation of multicellular cross-talk. In this review, we discuss protease regulation mechanisms of cytokine signalling in various types of cancer. Additionally, we highlight the reverse whereby cytokines have an impact on protease expression in an autocrine and paracrine manner, representing complex feedback mechanisms among multiple members of these two protein families. The relevance of the protease-cytokine axis is illustrated in glioblastoma, where interactions between normal mesenchymal stem cells and cancer cells play an important role in this very malignant form of brain cancer.

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Pericellular proteolysis in cancer

Cited by 160 publications

References 211 publications

Nicotine enhances invasion and metastasis of human colorectal cancer cells through the nicotinic acetylcholine receptor downstream p38 MAPK signaling pathway

Nicotine enhances invasion and metastasis of human colorectal cancer cells through the nicotinic acetylcholine receptor downstream p38 MAPK signaling pathway

Distinct functions of macrophage-derived and cancer cell-derived cathepsin Z combine to promote tumor malignancy via interactions with the extracellular matrix

Proteases and cytokines as mediators of interactions between cancer and stromal cells in tumours

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