Forced downregulation of RACK1 inhibits glioma development by suppressing Src/Akt signaling activity

Peng, Renjun; Jiang, Bing; Ma, Jingfei; Ma, Zhiming; Wan, Xin; Liu, Hongwei; Chen, Zigui; Cheng, Quan; Chen, Rui

doi:10.3892/or.2013.2723

Cited by 26 publications

(12 citation statements)

References 29 publications

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“…AKT is considered as an important key protein regulating tumor progression in various types of human cancer. Peng et al showed knocking down RACK1 in vitro decreased AKT activity in glioma (37). We further investigated whether RACK1 expression and AKT activation are relevant in human OSCC cell lines and clinical samples.…”

Section: Rack1 Silencing Induces G1 and G2 Phase Cell Cycle Arrestmentioning

confidence: 93%

Receptor for activated C kinase 1 (RACK1) promotes the progression of OSCC via the AKT/mTOR pathway

Zhang¹,

Liu²,

Ma³

et al. 2016

International Journal of Oncology

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Our previous study suggested that receptor for activated C kinase 1 (RACK1) contribute to the progression of oral squamous cell carcinoma (OSCC). The aim of this study is to elucidate the mechanism by which RACK1 regulates cell growth in OSCC using in vitro and in vivo models. The effects of RACK1 knockdown with lentivirus based shRNA in stable cell lines were evaluated by Q-PCR and western blot analysis. RACK1 silencing effects on the cell cycle in OSCC cells were detected by flow cytometry and western blot analysis. The effect of RACK1 silencing on inhibiting the progression of OSCC was illustrated using a xenografted mouse model. RACK1 and relevant signaling pathways were investigated in tissues and cells using immunohistochemistry and/or western blot analysis. Stable silencing of the RACK1 gene resulted in a distinct G1 and G2 phase arrest by downregulating Cyclin B1 and Cyclin D1. Depleted RACK1 led to markedly decreased tumor volume and the expression of Ki67, CD34, and VEGF in vivo. The expression of RACK1 and p-AKT has a parallel pattern in different stages of oral carcinogenesis tissues. In addition, the protein level of RACK1 was positively correlated with p-AKT in OSCC tissue samples and cell lines. We found specific transient knockdown of RACK1 could downregulate the protein levels of p-AKT, p-mTOR, and p-S6 in a dose-dependent manner. This study demonstrates that RACK1-dependent OSCC growth and survival may be related to the increased activation of the AKT/mTOR/S6 pathway.

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Section: Rack1 Silencing Induces G1 and G2 Phase Cell Cycle Arrestmentioning

confidence: 93%

Receptor for activated C kinase 1 (RACK1) promotes the progression of OSCC via the AKT/mTOR pathway

Zhang¹,

Liu²,

Ma³

et al. 2016

International Journal of Oncology

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“…Bcl-2 is a potent suppressor of cell apoptosis, 46 while Bax is a proapoptotic member of the Bcl-2 protein family; overexpression of Bax indicates an apoptosis-inducing tendency. 47 Regardless of whether an extrinsic or intrinsic apoptotic pathway is activated, caspase-3 is always activated downstream of apoptotic pathways 48 and plays an important role in cell death.…”

Section: Effects Of Phase and Topography Of Tio 2 Nanotubes On Cell Amentioning

confidence: 99%

Nanoscale TiO2 nanotubes govern the biological behavior of human glioma and osteosarcoma cells

Tian¹,

Qin²,

Wu³

et al. 2015

IJN

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Cells respond to their surroundings through an interactive adhesion process that has direct effects on cell proliferation and migration. This research was designed to investigate the effects of TiO 2 nanotubes with different topographies and structures on the biological behavior of cultured cells. The results demonstrated that the nanotube diameter, rather than the crystalline structure of the coatings, was a major factor for the biological behavior of the cultured cells. The optimal diameter of the nanotubes was 20 nm for cell adhesion, migration, and proliferation in both glioma and osteosarcoma cells. The expression levels of vitronectin and phosphor-focal adhesion kinase were affected by the nanotube diameter; therefore, it is proposed that the responses of vitronectin and phosphor-focal adhesion kinase to the nanotube could modulate cell fate. In addition, the geometry and size of the nanotube coating could regulate the degree of expression of acetylated α-tubulin, thus indirectly modulating cell migration behavior. Moreover, the expression levels of apoptosis-associated proteins were influenced by the topography. In conclusion, a nanotube diameter of 20 nm was the critical threshold that upregulated the expression level of Bcl-2 and obviously decreased the expression levels of Bax and caspase-3. This information will be useful for future biomedical and clinical applications.

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“…RACK1 expression varies in different cancer types (13). It is up-regulated in most cancer types, such as hepatocellular carcinoma (35,36), non-small-cell lung cancer (37), and glioma (38), but decreased in gastric cancer (17). Deregulation of Wnt signaling has been observed in multiple tumors, especially in colon cancer, and we have reported that Dvl expression is negatively correlated with autophagy in the late stage of colon cancer development (10).…”

Section: Discussionmentioning

confidence: 82%

Receptor for Activated C Kinase 1 (RACK1) Promotes Dishevelled Protein Degradation via Autophagy and Antagonizes Wnt Signaling

Cheng

Xue

Cao

et al. 2016

Journal of Biological Chemistry

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Wnt signaling plays a critical role in embryonic development, tissue homeostasis, and cancer development. Dishevelled (Dvl) is an essential and central component in Wnt signaling, and its stability and activity is tightly regulated. It has been shown that Dvl can be degraded via both the proteasome and autophagylysosome pathways. Here we report that receptor for activated C kinase 1 (RACK1) negatively regulates Dishevelled stability and Wnt signaling. RACK1 interacts with Dvl proteins and promotes their lysosomal degradation, and this effect is enhanced by autophagy induction. RACK1 also interacts with LC3 and enhances the association of LC3 with Dvl2, thereby leading to degradation of Dvl proteins through autophagy. These findings reveal a novel regulatory function of RACK1 in Wnt signaling by modulating Dvl stability.

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Forced downregulation of RACK1 inhibits glioma development by suppressing Src/Akt signaling activity

Cited by 26 publications

References 29 publications

Receptor for activated C kinase 1 (RACK1) promotes the progression of OSCC via the AKT/mTOR pathway

Receptor for activated C kinase 1 (RACK1) promotes the progression of OSCC via the AKT/mTOR pathway

Nanoscale TiO2 nanotubes govern the biological behavior of human glioma and osteosarcoma cells

Receptor for Activated C Kinase 1 (RACK1) Promotes Dishevelled Protein Degradation via Autophagy and Antagonizes Wnt Signaling

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