Procaspase-3 regulates fibronectin secretion and influences adhesion, migration and survival independent of catalytic function

Brentnall, Matthew; Weir, David B.; Rongvaux, Anthony; Marcus, Adam I.; Boise, Lawrence H.

doi:10.1242/jcs.135137

Cited by 30 publications

(39 citation statements)

References 45 publications

(47 reference statements)

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“…Little is known regarding FN secretion. A recent report has demonstrated that caspase 3 controls FN secretion without affecting FN1 expression [29]. The authors hypothesised that caspase 3 controls the ER-Golgi transport or vesicle trafficking.…”

Section: Discussionmentioning

confidence: 99%

Uncovering and deciphering the pro-invasive role of HACE1 in melanoma cells

et al. 2018

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HACE1 is an E3 ubiquitin ligase described as a tumour suppressor because HACE1-knockout mice develop multi-organ, late-onset cancers and because HACE1 expression is lost in several neoplasms, such as Wilms' tumours and colorectal cancer. However, a search of public databases indicated that HACE1 expression is maintained in melanomas. We demonstrated that HACE1 promoted melanoma cell migration and adhesion in vitro and was required for mouse lung colonisation by melanoma cells in vivo. Transcriptomic analysis of HACE1-depleted melanoma cells revealed an inhibition of ITGAV and ITGB1 as well changes in other genes involved in cell migration. We revealed that HACE1 promoted the K27 ubiquitination of fibronectin and regulated its secretion. Secreted fibronectin regulated ITGAV and ITGB1 expression, as well as melanoma cell adhesion and migration. Our findings disclose a novel molecular cascade involved in the regulation of fibronectin secretion, integrin expression and melanoma cell adhesion. By controlling this cascade, HACE1 displays pro-tumoural properties and is an important regulator of melanoma cell invasive properties.

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Section: Discussionmentioning

confidence: 99%

Uncovering and deciphering the pro-invasive role of HACE1 in melanoma cells

et al. 2018

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“…Taken together, procaspase‐3, not the catalytically active form of caspase‐3, is considered to play a critical role in the appropriate maintenance of mitochondrial biogenesis. Our novel discovery of the role of procaspase‐3 in mitochondrial biogenesis further suggests the expansive roles of caspases other than in cell death, including the other non‐apoptotic roles of caspase‐3 in cell differentiation [Ishizaki et al, ; Fernando et al, ; Miura et al, ; Okuyama et al, Fujita et al, ] and regulation of cell morphology, adhesion and migration [Brentnall et al, ], and other non‐apoptotic functions [Shalini et al, ].…”

Section: Discussionmentioning

confidence: 99%

A Novel Non‐Apoptotic Role of Procaspase‐3 in the Regulation of Mitochondrial Biogenesis Activators

Kim

Yang

et al. 2017

J of Cellular Biochemistry

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The executioner caspase-3 has been proposed as a pharmacological intervention target to preserve degenerating dopaminergic (DA) neurons because apoptotic mechanisms involving caspase-3 contribute, at least in part, to the loss of DA neurons in patients and experimental models of Parkinson's disease (PD). Here, we determined that genetic intervention of caspase-3 was sufficient to prevent cell death against oxidative stress (OS), accompanied by unexpected severe mitochondrial dysfunction. Specifically, as we expected, caspase-3-deficient DA neuronal cells were very significantly resistant to OS-induced cell death, while the activation of the initiator caspase-9 by OS was preserved. Moreover, detailed phenotypic characterization of caspase-3-deficient DA cells revealed severe mitochondrial dysfunction, including an accumulation of damaged mitochondria with a characteristic swollen structure and broken cristae, reduced membrane potential, increased levels of reactive oxygen species (ROS), and deficits in mitochondrial oxidative phosphorylation (OXPHOS) enzymes. Of great interest, we found that mitochondrial biogenesis was dramatically decreased in caspase-3-deficient DA cells, whereas their capability of mitophagy was normal. In accordance with this observation, caspase-3 gene knock down (KD) resulted in dramatically decreased expression of the key transcriptional activators of mitochondrial biogenesis, such as Tfam and Nrf-1, implicating a non-apoptotic role of procaspase-3 in mitochondrial biogenesis. Therefore, a prolonged anti-apoptotic intervention targeting caspase-3 should be considered with caution due to the potential adverse effects in mitochondria dynamics resulting from a novel potential functional role of procaspase-3 in mitochondrial biogenesis via regulating the expression of mitochondrial biogenesis activators. J. Cell. Biochem. 119: 347-357, 2018. © 2017 Wiley Periodicals, Inc.

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“…The possibility that FN overexpression accounts for normal epithelial senescence caused by various types of stresses [118][119][120][121][122][123] is substantially supported by the findings that silencing FN transcription or depleting periFN of pre-cancerous cells or pre-malignant tumor cells promotes characteristics of tumor progression, including proliferation, migration/invasion, tumor sizes, anchorage-independent cell growth, and angiogenesis [53,[64][65][66][67]106,[124][125][126][127]. Whether the promotion of tumor malignancy by FN depletion is due to the suppression of senescent phenotypes warrants further investigation.…”

Section: The Role Of Fn Expression In Epithelial Cell Senescence and mentioning

confidence: 99%

Fibronectin in Cancer: Friend or Foe

Lin

Yang

et al. 2019

Cells

133

117

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The role of fibronectin (FN) in tumorigenesis and malignant progression has been highly controversial. Cancerous FN plays a tumor-suppressive role, whereas it is pro-metastatic and associated with poor prognosis. Interestingly, FN matrix deposited in the tumor microenvironments (TMEs) promotes tumor progression but is paradoxically related to a better prognosis. Here, we justify how FN impacts tumor transformation and subsequently metastatic progression. Next, we try to reconcile and rationalize the seemingly conflicting roles of FN in cancer and TMEs. Finally, we propose future perspectives for potential FN-based therapeutic strategies. Figure 1. (A) The structure of fibronectin (FN) containing three types of repeats and three alternative splicing regions (EDA, EDB, and IIICS) with several well-known binding sites for extracellular matrix (ECM) components (fibrin, heparin, collagen, and gelatin), polymeric assembly (FN-FN), cell adhesion (integrin α5β1), DPP IV, and two C-terminal disulfide bonds for dimeric FN. (B) Publications in recent some forty years regarding the roles of cancerous FN and stromal FN in ECM in tumor progression as represented in a time-line pattern. Among 26 publications before 2000, 15 (57.7%) papers are related to the role of cancerous FN in tumor suppression (in light green boxes), 3 (11.5%) papers are related to the role of cancerous FN in metastasis promotion (in orange boxes), and 8 (30.8%) papers are related to the role of stromal FN in promoting early tumor progression but not late metastasis (in dark green boxes). On the contrary, Among 46 publications after 2000, 7 (15.2%) papers are related to the role of cancerous FN in tumor suppression (in light green boxes), 25 (54.4%) papers are related to the role of cancerous FN in metastasis promotion (in orange boxes), and 14 (30.4%) papers are related to the role of stromal FN in promoting early tumor progression but not late metastasis (in dark green boxes). Abbreviations in boxes are referred to the context of this article. (C) Percentages of articles for the three various roles of FN (the same colors as depicted in (B) before 2000 and after 2000. Numbers in the parenthesis represent article numbers. The Pathobiology of CancerFigure 1. (A) The structure of fibronectin (FN) containing three types of repeats and three alternative splicing regions (EDA, EDB, and IIICS) with several well-known binding sites for extracellular matrix (ECM) components (fibrin, heparin, collagen, and gelatin), polymeric assembly (FN-FN), cell adhesion (integrin α5β1), DPP IV, and two C-terminal disulfide bonds for dimeric FN. (B) Publications in recent some forty years regarding the roles of cancerous FN and stromal FN in ECM in tumor progression as represented in a time-line pattern. Among 26 publications before 2000, 15 (57.7%) papers are related to the role of cancerous FN in tumor suppression (in light green boxes), 3 (11.5%) papers are related to the role of cancerous FN in metastasis promotion (in orange boxes), and 8 (30.8%) papers are related to the r...

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Procaspase-3 regulates fibronectin secretion and influences adhesion, migration and survival independent of catalytic function

Cited by 30 publications

References 45 publications

Uncovering and deciphering the pro-invasive role of HACE1 in melanoma cells

Uncovering and deciphering the pro-invasive role of HACE1 in melanoma cells

A Novel Non‐Apoptotic Role of Procaspase‐3 in the Regulation of Mitochondrial Biogenesis Activators

Fibronectin in Cancer: Friend or Foe

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