Gravin gene expression in acute leukaemias: Clinical importance and review of the literature

Yıldırım, Mustafa; Paydaş, Semra; Tanrıverdi, Kahraman; Seydaoğlu, Gülşah; Dişel, Umut; Yavuz, Sinan

doi:10.1080/10428190701377055

Cited by 16 publications

(9 citation statements)

References 17 publications

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“…Such observations fit with reports that AKAP12 has been reported to act as a tumour suppressor that blocks the cell cycle and inhibits oncogenic proliferation, invasion, chemotaxis and neovascularization . However, the situation is not at all clear as the expression of the protein is higher in cancer cells which would tend to indicate a positive role in proliferation . Although the role of AKAP12 in endothelial cells has been studied, experiments have concentrated on dermal endothelial cells, as well as immortalized cells and the role of AKAP12 on permeability—little has been done to assess the consequences of AKAP12 on angiogenesis.…”

Section: Introductionsupporting

confidence: 80%

AKAP12 deficiency impairs VEGF‐induced endothelial cell migration and sprouting

et al. 2019

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Aim Protein kinase (PK) A anchoring protein (AKAP) 12 is a scaffolding protein that anchors PKA to compartmentalize cyclic AMP signalling. This study assessed the consequences of the downregulation or deletion of AKAP12 on endothelial cell migration and angiogenesis. Methods The consequences of siRNA‐mediated downregulation AKAP12 were studied in primary cultures of human endothelial cells as well as in endothelial cells and retinas from wild‐type versus AKAP12−/− mice. Molecular interactions were investigated using a combination of immunoprecipitation and mass spectrometry. Results AKAP12 was expressed at low levels in confluent endothelial cells but its expression was increased in actively migrating cells, where it localized to lamellipodia. In the postnatal retina, AKAP12 was expressed by actively migrating tip cells at the angiogenic front, and its deletion resulted in defective extension of the vascular plexus. In migrating endothelial cells, AKAP12 was co‐localized with the PKA type II‐α regulatory subunit as well as multiple key regulators of actin dynamics and actin filament‐based movement; including components of the Arp2/3 complex and the vasodilator‐stimulated phosphoprotein (VASP). Fitting with the evidence of a physical VASP/AKAP12/PKA complex, it was possible to demonstrate that the VEGF‐stimulated and PKA‐dependent phosphorylation of VASP was dependent on AKAP12. Indeed, AKAP12 colocalized with phospho‐Ser157 VASP at the leading edge of migrating endothelial cells. Conclusion The results suggest that compartmentalized AKAP12/PKA signalling mediates VASP phosphorylation at the leading edge of migrating endothelial cells to translate angiogenic stimuli into altered actin dynamics and cell movement.

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Section: Introductionsupporting

confidence: 80%

AKAP12 deficiency impairs VEGF‐induced endothelial cell migration and sprouting

et al. 2019

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“…Due to the fact that Rho GTPases are crucial for the coordination of events required for cell migration [61], this correlates well with the predicted increase of metastatic potential in the absence of NCOR1. AKAP12 has also been described as being induced in colon cancer cells [62]. Another report showed that overexpression of AKAP12 in a CRC cell line inhibited proliferation and anchorage-independent growth, features that correlate well with our observations [63].…”

Section: Discussionsupporting

confidence: 91%

NCOR1 Sustains Colorectal Cancer Cell Growth and Protects against Cellular Senescence

St-Jean

Castro

Lecours

et al. 2021

Cancers

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NCOR1 is a corepressor that mediates transcriptional repression through its association with nuclear receptors and specific transcription factors. Some evidence supports a role for NCOR1 in neonatal intestinal epithelium maturation and the maintenance of epithelial integrity during experimental colitis in mice. We hypothesized that NCOR1 could control colorectal cancer cell proliferation and tumorigenicity. Conditional intestinal epithelial deletion of Ncor1 in ApcMin/+ mice resulted in a significant reduction in polyposis. RNAi targeting of NCOR1 in Caco-2/15 and HT-29 cell lines led to a reduction in cell growth, characterized by cellular senescence associated with a secretory phenotype. Tumor growth of HT-29 cells was reduced in the absence of NCOR1 in the mouse xenografts. RNA-seq transcriptome profiling of colon cancer cells confirmed the senescence phenotype in the absence of NCOR1 and predicted the occurrence of a pro-migration cellular signature in this context. SOX2, a transcription factor essential for pluripotency of embryonic stem cells, was induced under these conditions. In conclusion, depletion of NCOR1 reduced intestinal polyposis in mice and caused growth arrest, leading to senescence in human colorectal cell lines. The acquisition of a pro-metastasis signature in the absence of NCOR1 could indicate long-term potential adverse consequences of colon-cancer-induced senescence.

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“…Roughly 40% of the Gleason sum 7 to 10 lesions that were deficient AKAP12 staining also exhibited gene deletion, as determined by laser capture microdissection followed by PCR analysis (AKAP12 and GAPDH control primers) (Gelman, unpublished data). Reports showing cancer-related loss of AKAP12 expression include human and rat prostate cancer cell lines, 36 pulmonary adenocarcinomas, 73 leiomymoma, 74 chronic and acute myeloid leukemias and myelodysplastic syndromes, 75-77 multiple myelomas, 78 papillary thyroid carcinoma, 79 pediatric acute lymphoblastic leukemia, 80 gastric cancer, 70 non-small cell lung carcinoma, 81 osteosarcomas, 82,83 melanomas, 84,85 retinoblastomas, 86 colon cancer, 87,88 fibrosarcomas, 89 and squamous cell lung carcinoma. 90,91 In all these cases, AKAP12 transcript levels are suppressed 5- to 15-fold compared to matched controls.…”

Section: Downregulation Of Akap12 In Human Cancersmentioning

confidence: 99%

“…90,91 In all these cases, AKAP12 transcript levels are suppressed 5- to 15-fold compared to matched controls. Many microarray-based studies demonstrate 3- to 10-fold reduction in relative AKAP12 mRNA levels in breast, prostate, lung, and ovarian cancers and in gliomas, 77,92-100 and others have been cited in Entrez GEO (Gene Expression Omnibus; www.ncbi.nlm.nih.gov/geo) or Oncomine (www.oncomine.org) linking AKAP12 expression with tumor suppression. In silico analyses at the Cancer Genome Anatomy Project SAGE (Serial Analysis of Gene Expression) site (http://cgap.nci.nih.gov/SAGE) identify AKAP12 downregulation in human thyroid, lung, and liver cancer tissue and in human ovarian cancer cell lines.…”

Section: Downregulation Of Akap12 In Human Cancersmentioning

confidence: 99%

Emerging Roles for SSeCKS/Gravin/AKAP12 in the Control of Cell Proliferation, Cancer Malignancy, and Barriergenesis

Gelman

2010

Genes & Cancer

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Emerging data suggest that SSeCKS/Gravin/AKAP12 (“AKAP12”), originally identified as an autoantigen in cases of myasthenia gravis, controls multiple biological processes through its ability to scaffold key signaling proteins such as protein kinase (PK) C and A, calmodulin, cyclins, phosphoinositides, the so-called “long” β-1,4 galactosyltransferase (GalTase) isoform, Src, as well as the actin cytoskeleton in a spatiotemporal manner. Specialized functions attributed to AKAP12 include the suppression of cancer malignancy- especially aspects of metastatic progression, regulation of blood-brain and blood-retina barrier formation, and re-sensitization of β2-adrenergic pain receptors. Recent data identify a direct role for AKAP12 in cytokinesis completion, further suggesting a function as a negative regulator of cell senescence. The current review will discuss the emerging knowledge base of AKAP12-related biological roles, and how the factors that affect AKAP12 expression or that interact with AKAP12 at the protein level control cancer progression and blood-tissue barrier formation.

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Gravin gene expression in acute leukaemias: Clinical importance and review of the literature

Cited by 16 publications

References 17 publications

AKAP12 deficiency impairs VEGF‐induced endothelial cell migration and sprouting

AKAP12 deficiency impairs VEGF‐induced endothelial cell migration and sprouting

NCOR1 Sustains Colorectal Cancer Cell Growth and Protects against Cellular Senescence

Emerging Roles for SSeCKS/Gravin/AKAP12 in the Control of Cell Proliferation, Cancer Malignancy, and Barriergenesis

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