Depletion of K-Ras promotes proteasome degradation of survivin

Tecleab, Awet; Sebti, Saı̈d M.

doi:10.4161/cc.23407

Cited by 14 publications

(18 citation statements)

References 35 publications

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“…After checking survivin depletion by Western Blot analysis, we found that the expression of Ha-Ras G12V -IκBαM in keratinocytes promoted survivin upregulation ( Figure 3 A), which is in line with the induction of the oncogenic phenotype in keratinocytes and the higher level of survivin in cancer cells [ 42 ]. This is also in agreement with Ras-dependent upregulation of survivin in HaCaT cells [ 43 , 44 ] and normal K-Ras promoted survivin degradation [ 45 ].…”

Section: Resultssupporting

confidence: 83%

Survivin Modulates Squamous Cell Carcinoma-Derived Stem-Like Cell Proliferation, Viability and Tumor Formation in Vivo

Lotti

Palazzo

Petrachi

et al. 2016

IJMS

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Squamous Cell Carcinoma-derived Stem-like Cells (SCC-SC) originate from alterations in keratinocyte stem cells (KSC) gene expression and sustain tumor development, invasion and recurrence. Since survivin, a KSC marker, is highly expressed in SCC-SC, we evaluate its role in SCC-SC cell growth and SCC models. Survivin silencing by siRNA decreases clonal growth of SCC keratinocytes and viability of total, rapidly adhering (RAD) and non-RAD (NRAD) cells from primary SCC. Similarly, survivin silencing reduces the expression of stem cell markers (OCT4, NOTCH1, CD133, β1-integrin), while it increases the level of differentiation markers (K10, involucrin). Moreover, survivin silencing improves the malignant phenotype of SCC 3D-reconstruct, as demonstrated by reduced epidermal thickness, lower Ki-67 positive cell number, and decreased expression of MMP9 and psoriasin. Furthermore, survivin depletion by siRNA in RasG12V-IκBα-derived tumors leads to smaller tumor formation characterized by lower mitotic index and reduced expression of the tumor-associated marker HIF1α, VEGF and CD51. Therefore, our results indicate survivin as a key gene in regulating SCC cancer stem cell formation and cSCC development.

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Section: Resultssupporting

confidence: 83%

Survivin Modulates Squamous Cell Carcinoma-Derived Stem-Like Cell Proliferation, Viability and Tumor Formation in Vivo

Lotti

Palazzo

Petrachi

et al. 2016

IJMS

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“…Caspases are blocked by inhibitors of apoptosis proteins (IAPs) like Xiap and Survivin downstream of this extrinsic and intrinsic apoptosis induction [ 16 , 17 ]. Furthermore, overexpression of these five anti-apoptotic genes in PDAC is facilitated by mutated KRAS via feedback loops or by inhibition of their antagonists [ 18 – 20 ].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous gene silencing of KRAS and anti-apoptotic genes as a multitarget therapy

et al. 2015

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Pancreatic cancer is one of the most lethal tumor types worldwide and an effective therapy is still elusive. Targeted therapy focused against a specific alteration is by definition unable to attack broad pathway signaling modification. Tumor heterogeneity will render targeted therapies ineffective based on the regrowth of cancer cell sub-clones. Therefore multimodal therapy strategies, targeting signaling pathways simultaneously should improve treatment.SiRNAs against KRAS and the apoptosis associated genes BCLXL, FLIP, MCL1L, SURVIVIN and XIAP were transfected into human and murine pancreatic cancer cell lines. Induction of apoptosis was measured by Caspase 3/7 activation, subG1 FACS analysis and PARP cleavage. The therapeutic approach was tested in a subcutaneous allograft model with a murine cancer cell line.By using siRNAs as a systematic approach to remodel signal transduction in pancreatic cancer the results showed increasing inhibition of proliferation and apoptosis induction in vitro and in vivo. Thus, siRNAs are suitable to model multimodal therapy against signaling pathways in pancreatic cancer. Improvements in in vivo delivery of siRNAs against a multitude of targets might therefore be a potential therapeutic approach.

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“…Survivin is also regulated by XIAP-XAF1 complex 28 . Tecleab et al have reported that depletion of K-Ras promotes proteasome degradation of survivin 29 . Proteasome subunits of PSMA5 and PSMD4/S5a play a critical role in proteasomal activity.…”

Section: Discussionmentioning

confidence: 99%

Galangin sensitizes TRAIL-induced apoptosis through down-regulation of anti-apoptotic proteins in renal carcinoma Caki cells

Han

Lee

Woo

et al. 2016

Sci Rep

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Galangin, bioflavonoids, has been shown anti-cancer properties in various cancer cells. In this study, we investigated whether galangin could enhance TRAIL-mediated apoptosis in TRAIL resistant renal carcinoma Caki cells. Galangin alone and TRAIL alone had no effect on apoptosis, while combined treatment with galangin and TRAIL significantly induced apoptosis in renal carcinoma (Caki, ACHN and A498) but not normal cells (normal mouse kidney cells and human normal mesangial cells). Galangin induced down-regulation of Bcl-2 protein at the transcriptional level via inhibition of NF-κB activation but not p53 pathway. Furthermore, galangin induced down-regulation of cFLIP, Mcl-1 and survivin expression at the post-translational levels, and the over-expression of Bcl-2, cFLIP, Mcl-1 and survivin markedly reduced galangin-induced TRAIL sensitization. In addition, galangin increased proteasome activity, but galangin had no effect on expression of proteasome subunits (PSMA5 and PSMD4). In conclusion, our investigation suggests that galangin is a potent candidate for sensitizer of TRAIL resistant cancer cell therapy.

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Depletion of K-Ras promotes proteasome degradation of survivin

Cited by 14 publications

References 35 publications

Survivin Modulates Squamous Cell Carcinoma-Derived Stem-Like Cell Proliferation, Viability and Tumor Formation in Vivo

Survivin Modulates Squamous Cell Carcinoma-Derived Stem-Like Cell Proliferation, Viability and Tumor Formation in Vivo

Simultaneous gene silencing of KRAS and anti-apoptotic genes as a multitarget therapy

Galangin sensitizes TRAIL-induced apoptosis through down-regulation of anti-apoptotic proteins in renal carcinoma Caki cells

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