Rho/ROCK/actin signaling regulates membrane androgen receptor induced apoptosis in prostate cancer cells

Papadopoulou, Natalia; Charalampopoulos, Ioannis; Alevizopoulos, Konstantinos; Gravanis, Achille; Stournaras, Christos

doi:10.1016/j.yexcr.2008.07.012

Cited by 58 publications

(91 citation statements)

References 49 publications

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“…4,5 On the other hand, in DU145 prostate cancer cells, Rac1 activation was not observed, while the involvement of the RhoA/B/ROCK signaling was reported to be crucial for the regulation of actin restructuring and the potent pro-apoptotic response. 7 These findings further emphasize the central role of the family of small GTPases in regulating actin redistribution triggered by mAR activation in tumors. Interestingly, in a recent study in colon tumor cells, we have shown that Rho/ROCK signaling is not implicated in mAR signaling.…”

Section: Discussionmentioning

confidence: 77%

“…5,6,13,14 These effects were regulated by the mAR-governed actin reorganization. 7,12,13 Taken together, these studies clearly established that functional mARs trigger strong antitumorigenic effects, implying a potential role of mAR as a novel target for the development of selective cancer treatments. 8 The findings presented in the present study further support the significant role of mAR stimulated PI3K/Rac1 signaling in regulating actin reorganization and the apoptotic response in colon tumor cells.…”

Section: Discussionmentioning

confidence: 82%

“…1 Functional membrane androgen binding sites have been previously identified and characterized in human prostate and breast cancer cells. [2][3][4][5][6][7] Activation of these binding sites by no permeable testosterone albumin conjugates (TACs), was shown to induce strong proapoptotic and anti-tumorigenic effects on various tumors both in vitro and in vivo. 2,6,8,9 The molecular mechanisms governing these effects have been elucidated and specific signaling cascades triggered by the stimulation of membrane androgen receptors (mARs) have been described in prostate and breast tumor cells.…”

Section: Introductionmentioning

confidence: 99%

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Testosterone induced apoptosis in colon cancer cells is regulated by PI3K/Rac1 signaling

Alkahtani¹

2013

Asian J Androl

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Recently, it has been reported that testosterone membrane signaling regulates actin reorganization and induces pro-apoptotic responses in colon tumor cells. In the present study the membrane androgen receptors (mARs)-induced activation of Rac1 GTPase and the involvement of PI3K/Rac1 signaling in controlling the apoptotic responses in testosterone treated Caco2 colon cancer cells has been analyzed. In line with previous findings, activation of mAR by testosterone conjugates triggered early and transient actin reorganization as indicated by the significant decrease of the G/Total actin ratio after 15-and 30-min treatment of the cells. Interestingly, stimulation of mAR rapidly activated the Rac1 GTPase. This effect was evident after 15 min and persisted for at least 24 h. Testosterone induced Rac1 activation was fully blocked in Caco2 cells pre-treated with the PI3K inhibitor wortmannin, indicating that Rac1 signaling is acting downstream of the PI3K pathway. Remarkably, when cells were pre-treated with wortmannin that blocks the PI3K/Rac1 signaling, apoptotic response was almost fully inhibited. These finding suggest that Rac1 activation, triggering actin redistribution, is involved in testosterone induced pro-apoptotic responses governed by mAR activation and emphasize the regulatory role of PI3K/Rac1 signaling in colon tumors.

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

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Testosterone induced apoptosis in colon cancer cells is regulated by PI3K/Rac1 signaling

Alkahtani¹

2013

Asian J Androl

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“…Emerging evidence in recent years has indicated that actin remodeling is also involved in the regulation of apoptosis and specific signaling pathways regulating both, actin reorganization and the apoptotic response were elucidated (32,33). Our recent observations showing that actin reorganization triggered upon activation of membrane androgen receptors (mAR) controlled the apoptotic response of human prostate cancer cells (34) clearly establish a pivotal role of actin signaling linking mAR activation and regulation of pro-apoptotic mechanisms in different cancer cells.…”

Section: Introductionmentioning

confidence: 70%

“…These effects were clearly attributed to mAR activation and were independent of classical intracellular androgen receptors (iARs) because they were observed in the presence of the anti-androgen flutamide, or iAR anti-sense oligonucleotides (21). Analysis of the molecular signaling activated by mAR identified a novel mAR-specific non-genomic pathway operating in LNCaP cells (25,34). Initially, focal adhesion kinase (FAK) was rapidly phosphorylated and associated with the p85 subunit of the phosphoinositol-3-Kinase (PI-3K).…”

Section: Membrane Androgen Receptor Signaling In Human Cancer Cells Mmentioning

confidence: 99%

Membrane androgen receptor activation in prostate and breast tumor cells: Molecular signaling and clinical impact

et al. 2008

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In recent years, membrane androgen receptors (mARs) have been identified in prostate and breast tumor cells, and their activation by specific mAR ligands was linked to the regulation of crucial cell responses, such as cell growth, motility, and apoptosis. Analysis of the molecular signals triggered by mAR in the presence of anti‐androgens has clearly differentiated mAR‐dependent biological actions from those induced by the activation of the classical intracellular androgen receptors (iARs). In this review, we summarize the specific cellular events attributed to mAR activation and the experimental results on distinct non‐genomic signaling cascades operating in various tumor cells independently of the iAR. Furthermore, we discuss the crucial role of actin cytoskeleton organization and signaling in mediating mAR responses. Finally, we assess the clinical impact of the reported mAR‐induced apoptotic regression of prostate cancer cells both in vitro and in vivo and discuss the potential role of mAR as a novel therapeutic target. © 2008 IUBMB IUBMB Life, 61(1): 56–61, 2009

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Fibroblast growth factor (Fgf) 23 gene transcription depends on actin cytoskeleton reorganization

et al. 2016

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Edited by Lukas Alfons HuberThe consequence is a decrease in the plasma concentration of phosphate and 1,25(OH) 2 D 3 , the biologically active form of vitamin D. To mediate these renal effects, FGF23 requires aKlotho as a co-receptor [4,5].In addition, FGF23 is a powerful counteracter of aging. Mice deficient for FGF23 or for aKlotho suffer from rapid aging with a life span of a few weeks only and numerous age-related diseases [5,6]. The rapid aging is directly or indirectly dependent on the hyperphosphatemia of the mice as feeding them a low-phosphate or low-vitamin D diet greatly expands their life span [7].In contrast, excess FGF23 production due to FGF23-synthesizing tumors in men results in osteomalacia [8]. The regulation of FGF23 formation by bone cells has remained ill-defined. Among the known triggers of FGF23 expression are parathyroid hormone (PTH) [9][10][11], 1,25(OH) 2 D 3 [12,13] and increased dietary phosphorus intake [14,15]. Mutations of the dentin Abbreviations 1,25(OH) 2 D 3, calcitriol; Fgf, fibroblast growth factor; NFjB, nuclear factor kappa B; PI3, phosphoinositide-3; PTH, parathyroid hormone; PVDF, polyvinylidene fluoride; TNF, tumor necrosis factor; VDR, vitamin D receptor. 705FEBS Letters 590 (2016) 705-715 ª

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Rho/ROCK/actin signaling regulates membrane androgen receptor induced apoptosis in prostate cancer cells

Cited by 58 publications

References 49 publications

Testosterone induced apoptosis in colon cancer cells is regulated by PI3K/Rac1 signaling

Testosterone induced apoptosis in colon cancer cells is regulated by PI3K/Rac1 signaling

Membrane androgen receptor activation in prostate and breast tumor cells: Molecular signaling and clinical impact

Fibroblast growth factor (Fgf) 23 gene transcription depends on actin cytoskeleton reorganization

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