Procathepsin D secreted by HaCaT keratinocyte cells – A novel regulator of keratinocyte growth

Vashishta, Aruna; Ohri, Sujata Saraswat; Větvičková, Jana; Fusek, Martin; Ulrichová, Jitka; Větvička, Václav

doi:10.1016/j.ejcb.2007.03.008

Cited by 21 publications

(21 citation statements)

References 49 publications

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“…Moreover, substantial secretion of pCD, up-regulated by stress conditions, was also observed in these cells [33]. These data suggest that enzymatically inactive pCD may serve as mitogenic factor for keratinocytes in a manner similar as that for cancer cells (discussed later).…”

Section: Mechanisms Of Neuronal and Retinal Cell Death In CD Knock-oumentioning

confidence: 57%

“…pCD and mature CD was also found in macrophage-conditioned media and extracellularly in macrophage-rich regions of atherosclerotic lesions [32]. We have recently demonstrated pCD secretion by human keratinocytes [33].…”

Section: Introductionmentioning

confidence: 97%

“…Recently, the growth-promoting effect of pCD was also described for fibroblasts [27] and keratinocytes [33]. While in the latter case the role of pCD in wound healing has been suggested, the role of pCD as paracrine communicator between cancer cells and stromal fibroblasts might be extremely important for cancer development.…”

Section: Cancer Cell Proliferationmentioning

confidence: 99%

“…While many functions of CD in the physiological and pathological processes could be attributed to its enzymatic activity, it is evident that some of its functions in the organism are independent on its protease activity and rely on the ability of pCD/CD to interact with other important molecules (Tab 2) [27,33,120,124,130,186,194,212,220]. It seems inevitable that searching for pCD/CD-interacting partners should be conducted in the next years to explore the mechanism of pCD/CD actions.…”

Section: Future Prospectsmentioning

confidence: 99%

“…Activation of neutrophils and leukocytes [220] Regulation of apoptosis [27,120,124] Mitogenicity -cancer cells, fibroblasts, keratinocytes [27,33,194,212] Wound healing [33] Tumor angiogenesis [130] Tumor invasion -cancer cells, fibroblasts [27,186] …”

Section: Biological Function Referencementioning

confidence: 99%

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Cathepsin D—Many functions of one aspartic protease

Beneš

Větvička

Fusek

2008

Critical Reviews in Oncology/Hematology

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532

474

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For years, it has been held that cathepsin D (CD) is involved in rather nonspecific protein degradation in a strongly acidic milieu of lysosomes. Studies with CD knock-out mice revealed that CD is not necessary for embryonal development but it is indispensable for postnatal tissue homeostasis. Mutation that abolishes CD enzymatic activity causes neuronal ceroid lipofuscinosis (NCL) characterized by severe neurodegeneration, developmental regression, visual loss and epilepsy in both animals and humans.In the last decade, however, an increasing number of studies demonstrated that enzymatic function of CD is not restricted solely to acidic milieu of lysosomes with important consequences in regulation of apoptosis. In addition to CD enzymatic activity, it has been shown that apoptosis is also regulated by catalytically inactive mutants of CD which suggests that CD interacts with other important molecules and influences cell signaling.Moreover, procathepsin D, secreted from cancer cells, acts as a mitogen on both cancer and stromal cells and stimulates their pro-invasive and pro-metastatic properties. Numerous studies found that pCD/CD level represents an independent prognostic factor in a variety of cancers and is therefore considered to be a potential target of anti-cancer therapy.Studies dealing with functions of cathepsin D are complicated by the fact that there are several simultaneous forms of CD in a cell -pCD, intermediate enzymatically active CD and mature heavy and light chain CD. It became evident that these forms may differently regulate the above mentioned processes.In this article, we review the possible functions of CD and its various forms in cells and organisms during physiological and pathological conditions.

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Section: Mechanisms Of Neuronal and Retinal Cell Death In CD Knock-oumentioning

confidence: 57%

Section: Introductionmentioning

confidence: 97%

Section: Cancer Cell Proliferationmentioning

confidence: 99%

Section: Future Prospectsmentioning

confidence: 99%

Section: Biological Function Referencementioning

confidence: 99%

See 3 more Smart Citations

Cathepsin D—Many functions of one aspartic protease

Beneš

Větvička

Fusek

2008

Critical Reviews in Oncology/Hematology

Self Cite

532

474

View full text Add to dashboard Cite

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Castration induces changes in the cation‐dependent mannose‐6‐phosphate receptor in rat epididymis: Possible implications in secretion of lysosomal enzymes

Carvelli

Bannoud

Aguilera

et al. 2010

J of Cellular Biochemistry

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It is believed that the mammalian epididymis participates in the maturation of the sperm due to its secretory activity. High concentrations of several secreted acid hydrolases are found in the epididymal lumen. Moreover, some of these enzymes are secreted by the epididymal epithelium in an androgen-dependent fashion. In this study, we attempted to discern whether mannose-6-phosphate receptors (MPRs) regulate transport and secretion of lysosomal enzymes in the rat epididymis, and if these events are altered when the animals are subjected to hormonal manipulation. We observed that expression of cation-dependent MPR (CD-MPR) and cation-independent MPR (CI-MPR) increased significantly in caudal epididymis of castrated rats by immunoblot. This increase was corroborated by quantitation of MPRs, by binding assays. This change could be due to androgen deprivation, as a similar effect was observed after treatment with the anti-androgenic drug flutamide. Furthermore, we observed that the CD-MPR was redistributed to the apical area of the epithelium on castrated rats by immunohistochemistry, which is compatible with the redistribution of the receptors toward lighter fractions in a Percoll gradient. Consistent with a possible involvement of the CD-MPR in the secretion, we observed an increase in pro-cathepsin D levels in epididymal fluid after castration. We conclude that the CD-MPR might be regulated by hormones and that this receptor might be involved in the secretion of specific enzymes into the rat epididymis.

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Skin aging caused by intrinsic or extrinsic processes characterized with functional proteomics

et al. 2016

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The skin provides protection against environmental stress. However, intrinsic and extrinsic aging causes significant alteration to skin structure and components, which subsequently impairs molecular characteristics and biochemical processes. Here, we have conducted an immunohistological investigation and established the proteome profiles on nude mice skin to verify the specific responses during aging caused by different factors. Our results showed that UVB-elicited aging results in upregulation of proliferating cell nuclear antigen and strong oxidative damage in DNA, whereas chronological aging abolished epidermal cell growth and increased the expression of caspase-14, as well as protein carbonylation. Network analysis indicated that the programmed skin aging activated the ubiquitin system and triggered obvious downregulation of 14-3-3 sigma, which might accelerate the loss of cell growth capacity. On the other hand, UVB stimulation enhanced inflammation and the risk of skin carcinogenesis. Collectively, functional proteomics could provide large-scale investigation of the potent proteins and molecules that play important roles in skin subjected to both intrinsic and extrinsic aging.

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Procathepsin D secreted by HaCaT keratinocyte cells – A novel regulator of keratinocyte growth

Cited by 21 publications

References 49 publications

Cathepsin D—Many functions of one aspartic protease

Cathepsin D—Many functions of one aspartic protease

Castration induces changes in the cation‐dependent mannose‐6‐phosphate receptor in rat epididymis: Possible implications in secretion of lysosomal enzymes

Skin aging caused by intrinsic or extrinsic processes characterized with functional proteomics

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