Role of E-cadherin in the induction of apoptosis of HPV16-positive CaSki cervical cancer cells during multicellular tumor spheroid formation

Haga, Takeshi; Uchide, Noboru; Tugizov, Sharof M.; Palefsky, Joel M.

doi:10.1007/s10495-007-0132-2

Cited by 13 publications

(9 citation statements)

References 39 publications

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“…This 100-kDa fragment, which was previously identified in prostate epithelial cells upon experimental calpain activation, is known to lack the capacity to bind to ␤-and ␥-catenin, in contrast to the full-length form of the protein (74). Moreover, in multicellular tumor spheroids (82) and in lymphovascular tumor emboli (71), the 100-kDa E-cadherin fragment was also discovered and attributed to endogenous activity of calpain (71). Another important finding of our study was the appearance of a 75-kDa ␤-catenin fragment under suspension culture conditions.…”

Section: Discussionmentioning

confidence: 94%

Cleavage of E-Cadherin and β-Catenin by Calpain Affects Wnt Signaling and Spheroid Formation in Suspension Cultures of Human Pluripotent Stem Cells

Konze

Diepen²,

Schröder

et al. 2014

Molecular & Cellular Proteomics

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The envisioned clinical and industrial use of human pluripotent stem cells and their derivatives has given major momentum to the establishment of suspension culture protocols that enable the mass production of cells. Understanding molecular changes accompanying the transfer from adherent to suspension culture is of utmost importance because this information can have a direct effect on the development of optimized culture conditions. In this study we assessed the gene expression of human embryonic stem cells and induced pluripotent stem cells grown in surface-adherent culture (two-dimensional) versus free-floating suspension culture spheroids (three-dimensional). We combined a quantitative proteomic approach based on stable isotope labeling by amino acids in cell culture with deep-sequencing-based transcriptomics. Cells in three-dimensional culture showed reduced expression of proteins forming structural components of cell-cell and cell-extracellular matrix junctions. However, fully unexpected, we found up-regulation of secreted inhibitors of the canonical Wnt signaling pathway and, concomitantly, a reduction in the level of active ␤-catenin and in the expression of Wnt target genes. In Western blot analyses the cysteine protease calpain was shown to cleave E-cadherin and ␤-catenin under three-dimensional culture conditions. Our data al- Human embryonic and induced pluripotent stem cells (hESCs and hiPSCs, respectively) 1 hold the potential for indefinite self-renewal and differentiation into all somatic cell types (1, 2). Beyond their application as models for studying mechanisms of pluripotency, these cells have been considered as a potent source for cell therapies and in vitro assays in pharmacology and toxicology, raising the need for largescale cell production under defined conditions (3). Conventional, surface adherent, two-dimensional culture is not suited to generate billions of human pluripotent stem cells (hPSCs) and their respective progenies required for clinical applications (3). To overcome these limits, three-dimensional culture From the ‡Institute for Cellular Chemistry, Hannover Medical School, 30625 Hannover, Germany; §REBIRTH Cluster of Excellence, Hannover Medical School, 30625 Hannover, Germany; ¶Institute for

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Section: Discussionmentioning

confidence: 94%

Cleavage of E-Cadherin and β-Catenin by Calpain Affects Wnt Signaling and Spheroid Formation in Suspension Cultures of Human Pluripotent Stem Cells

Konze

Diepen²,

Schröder

et al. 2014

Molecular & Cellular Proteomics

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“…Recently, the significant reduction of E-cadherin by regulation of HPV-16 E6 and/or E7 in cervical cell lines has been demonstrated extensively by many studies [28,29]. Furthermore, Haga et al also found that ectopic expression of HPV-16 E6 and E7 in normal epithelial cells in vitro resulted in decreased expression of E-cadherin and increased expression of N-cadherin although N-cadherin was not at readily detectable levels [30]. We therefore evaluated whether HR-HPV E6 and E7 could regulate cadherin switch in cervical cancer and contribute to tumor progression.…”

Section: Discussionmentioning

confidence: 98%

HPV-16 E6/E7 promotes cell migration and invasion in cervical cancer via regulating cadherin switch in vitro and in vivo

Zhou

Wang

et al. 2015

Arch Gynecol Obstet

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“…In non-cochlear tissues, adhesion proteins have been implicated in mediating signaling pathways in various pathological conditions, including cell detachment (Frisch and Screaton, 2001; Grossmann, 2002; Haga et al, 2008; Malik, 1997). The detachment of cells from their anchorage has been shown to be a trigger for apoptosis (Frisch, 2000).…”

Section: Introductionmentioning

confidence: 99%

Transcriptional changes in adhesion-related genes are site-specific during noise-induced cochlear pathogenesis

Cai¹,

Patel²,

Coling³

et al. 2012

Neurobiology of Disease

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Cell-cell junctions and junctions between cells and extracellular matrix are essential for maintenance of the structural and functional integrity of the cochlea, and are also a major target of acoustic trauma. While morphological assessments have revealed adhesion dysfunction in noise-traumatized cochleae, the molecular mechanisms responsible for adhesion disruption are not clear. Here, we screened the transcriptional expression of 49 adhesion-related genes in normal rat cochleae and measured the expression changes in the early phases of cochlear pathogenesis after acoustic trauma. We found that genes from four adhesion families, including the immunoglobulin superfamily and the integrin, cadherin, and selectin families, are expressed in the normal cochlea. Exposure to an intense noise at 120 dB sound pressure level (SPL) for 2 h caused site-specific changes in expression levels in the apical and the basal sections of the sensory epithelium. Expression changes that occurred in the cochlear sensory epithelium were biphasic, with early upregulation at 2 h post-noise exposure and subsequent downregulation at 1 day post-exposure. Importantly, the altered expression level of seven genes (Sgce, sell, Itga5, Itgal, Selp, Cntn1 and Col5a1) is related to the level of threshold shift of the auditory brainstem response (ABR), an index reflecting functional change in the cochlea. Notably, the genes showing expression changes exhibited diverse constitutive expression levels and belong to multiple adhesion gene families. The finding of expression changes in multiple families of adhesion genes in a temporal fashion (2 h vs. 1 day) and a spatial fashion (the apical and the basal sensory epithelia as well as the lateral wall tissue) suggests that acoustic overstimulation provokes a complex response in adhesion genes, which likely involves multiple adhesion-related signaling pathways.

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Role of E-cadherin in the induction of apoptosis of HPV16-positive CaSki cervical cancer cells during multicellular tumor spheroid formation

Cited by 13 publications

References 39 publications

Cleavage of E-Cadherin and β-Catenin by Calpain Affects Wnt Signaling and Spheroid Formation in Suspension Cultures of Human Pluripotent Stem Cells

Cleavage of E-Cadherin and β-Catenin by Calpain Affects Wnt Signaling and Spheroid Formation in Suspension Cultures of Human Pluripotent Stem Cells

HPV-16 E6/E7 promotes cell migration and invasion in cervical cancer via regulating cadherin switch in vitro and in vivo

Transcriptional changes in adhesion-related genes are site-specific during noise-induced cochlear pathogenesis

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