Regulator of calcineurin 1 modulates cancer cell migration in vitro

Espinosa, Allan V.; Shinohara, Motoo; Porchia, Leonardo M.; Chung, Yun Jae; McCarty, Samantha; Saji, Motoyasu; Ringel, Matthew D.

doi:10.1007/s10585-009-9251-1

Cited by 25 publications

(28 citation statements)

References 34 publications

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“…Alternatively, enhanced RCAN2 expression could result from attempts to suppress upregulated calcineurin-based signalling. Activation of NFAT signalling has been described to occur downstream of α6β4 integrin activation in metastatic cancer cells (Jauliac et al, 2002) and RCAN1 can modulate cancer cell migration (Espinosa et al, 2009). Of note, both giantin KO cells and giantin KO fish have substantial defects in extracellular matrix-related functions (Bergen et al, 2017;Stevenson et al, 2017).…”

Section: Results and Discussion Giantin Ko Cells Show No Gross Defectmentioning

confidence: 99%

Regulator of calcineurin-2 is a centriolar protein with a role in cilia length control

Stevenson

Bergen

et al. 2018

Journal of Cell Science

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Almost every cell in the human body extends a primary cilium. Defective cilia function leads to a set of disorders known as ciliopathies, which are characterised by debilitating developmental defects that affect many tissues. Here, we report a new role for regulator of calcineurin 2 (RCAN2) in primary cilia function. It localises to centrioles and the basal body and is required to maintain normal cilia length. RCAN2 was identified as the most strongly upregulated gene from a comparative RNAseq analysis of cells in which expression of the Golgi matrix protein giantin had been abolished by gene editing. In contrast to previous work where we showed that depletion of giantin by RNAi results in defects in ciliogenesis and in cilia length control, giantin knockout cells generate normal cilia after serum withdrawal. Furthermore, giantin knockout zebrafish show increased expression of RCAN2. Importantly, suppression of RCAN2 expression in giantin knockout cells results in the same defects in the control of cilia length that are seen upon RNAi of giantin itself. Together, these data define RCAN2 as a regulator of cilia function that can compensate for the loss of giantin function.

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Section: Results and Discussion Giantin Ko Cells Show No Gross Defectmentioning

confidence: 99%

Regulator of calcineurin-2 is a centriolar protein with a role in cilia length control

Stevenson

Bergen

et al. 2018

Journal of Cell Science

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“…Cells were pretreated with antibody for 30 min in suspension, then placed in the chambers and incubated at 37°C 5% CO 2 for 18–24 hrs. Migration was determined using the procedures of (42). Experiments were performed in duplicate on multiple occasions as described in the figure legends.…”

Section: Methodsmentioning

confidence: 99%

Potent Inhibition of Angiogenesis by the IGF-1 Receptor-Targeting Antibody SCH717454 Is Reversed by IGF-2

Bid

Zhan

Phelps

et al. 2012

Molecular Cancer Therapeutics

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Previously, we reported that a predominant action of an IGF-1R-targeted antibody was through inhibiting tumor-derived VEGF, and indirectly, angiogenesis. Here we examined the direct anti-angiogenic activity of the IGF-1R-targeted antibody SCH717454 that inhibits ligand-receptor binding, and the mechanism by which tumors circumvent its anti-angiogenic activity. Inhibition of ligand stimulated activation of IGF-1R, insulin receptor (IN-R) or downstream signaling (phosphorylation of Akt [Ser473]) was determined by receptor-specific immunoprecipitation and immunoblotting. Inhibition of angiogenesis was determined by proliferation and tube formation using human umbilical vein endothelial cells (HUVECs) in vitro and in Matrigel plugs implanted in mice. SCH717454 blocked IGF-1 but not IGF-2 stimulated phosphorylation of Akt in sarcoma cells. Immunoprecipitation using anti-IGF-1R and anti-IN-R antibodies revealed that SCH717454 equally blocked IGF-1 and IGF-2 stimulated IGF-1R phosphorylation, but not IGF-2 stimulated phosphorylation of IN-R. SCH717454 completely blocked VEGF-stimulated proliferation and tube formation of HUVECs, but exogenous IGF-2 and insulin circumvented these inhibitory effects. Co-culture of HUVECs with IGF-2-secreting tumor cells completely abrogated SCH717454 inhibition of VEGF-stimulated HUVEC tube formation. In mice SCH717454 inhibited angiogenesis in VEGF-infused Matrigel plugs, but had no inhibitory activity when plugs contained both VEGF+IGF-2. These results reveal for the first time, a role for IGF-1R signaling in VEGF-mediated angiogenesis in vitro and indicate direct anti-angiogenic activity of SCH717454. Both in vitro and in vivo IGF-2 circumvented these effects through IN-R signaling. Many childhood cancers secrete IGF-2, suggesting that tumor-derived IGF-2 in the microenvironment maintains angiogenesis in the presence of IGF-1R-targeted antibodies allowing tumor progression.

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“…HXR9 is cytotoxic to cells, predominantly through the induction of apoptosis, which in turn depends upon a rapid increase in expression of c-Fos. [124][125][126][127][128][129] It seems likely that AML would also be sensitive to killing by HXR9, and indeed it may be that the HOX genes could represent a useful therapeutic target, especially in AMLs that show high levels of HOX expression and a correspondingly poor prognosis.…”

Section: Future Directionsmentioning

confidence: 99%