Up-regulation of growth factor receptor-bound protein 10 in cervical squamous cell carcinoma

Okino, K.; Konishi, Hideyuki; Doi, Daisuke; Yoneyama, Kihei; Ota, Yujiro; Jin, Enjing; Kawanami, Oichi; Takeshita, Toshiyuki

doi:10.3892/or.13.6.1069

Cited by 14 publications

(12 citation statements)

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“…Despite the role of GRB10 as a signaling hub now being well explored, its role in cancer remains ill defined. Grb10 is reportedly deregulated in human osteosarcoma (33), metastatic malignant melanoma (34), cervical squamous carcinoma (35), acute myeloid anemia (36), and thyroid carcinoma (37), suggesting a role in tumorigenesis. In line with these earlier reports, we also observed increased expression of GRB10 in PCa, and knockdown of GRB10 results in loss of proliferation and retardation of migration in PCa cell lines, clearly confirming the tumorigenic role of GRB10 in PCa.…”

Section: Proproliferatve Role Of Grb10 In Pcamentioning

confidence: 99%

Proproliferative function of adaptor protein GRB10 in prostate carcinoma

et al. 2018

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Growth factor receptor‐binding protein 10 (GRB10) is a well‐known adaptor protein and a recently identified substrate of the mammalian target of rapamycin (mTOR). Depletion of GRB10 increases insulin sensitivity and overexpression suppresses PI3K/Akt signaling. Because the major reason for the limited efficacy of PI3K/Akt‐targeted therapies in prostate cancer (PCa) is loss of mTOR‐regulated feedback suppression, it is therefore important to assess the functional importance and regulation of GRB10 under these conditions. On the basis of these background observations, we explored the status and functional impact of GRB10 in PCa and found maximum expression in phosphatase and tensin homolog (PTEN)‐deficient PCa. In human PCa samples, GRB10 inversely correlated with PTEN and positively correlated with pAKT levels. Knockdown of GRB10 in nontumorigenic PTEN null mouse embryonic fibroblasts and tumorigenic PCa cell lines reduced Akt phosphorylation and selectively activated a panel of receptor tyrosine kinases. Similarly, overexpression of GRB10 in PTEN wild‐type PCa cell lines accelerated tumorigenesis and induced Akt phosphorylation. In PTEN wild‐type PCa, GRB10 overexpression promoted mediated PTEN interaction and degradation. PI3K (but not mTOR) inhibitors reduced GRB10 expression, suggesting primarily PI3K‐driven regulation of GRB10. In summary, our results suggest that GRB10 acts as a major downstream effector of PI3K and has tumor‐promoting effects in prostate cancer.—Khan, M. I., Al Johani, A., Hamid, A., Ateeq, B., Manzar, N., Adhami, V. M., Lall, R. K., Rath, S., Sechi, M., Siddiqui, I. A., Choudhry, H., Zamzami, M. A., Havighurst, T. C., Huang, W., Ntambi, J. M., Mukhtar, H. Proproliferatve function of adaptor protein GRB10 in prostate carcinoma. FASEB J. 33, 3198–3211 (2019). http://www.fasebj.org

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Section: Proproliferatve Role Of Grb10 In Pcamentioning

confidence: 99%

Proproliferative function of adaptor protein GRB10 in prostate carcinoma

et al. 2018

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“…With the recent identification of siRNA targets for cervical cancer (E6, E7 and Grb10) [14,46], HIV infections (CCR5) [47], or HSV-2 infections (UL-29 and UL-27) [3], vaginal application of siRNA has great appeal and importance. To our knowledge, this is the first report on the combined use of biodegradable scaffold and liposomes for mucosal delivery of siRNA.…”

Section: Resultsmentioning

confidence: 99%

Vaginal delivery of siRNA using a novel PEGylated lipoplex-entrapped alginate scaffold system

Chang

Burgess

et al. 2011

Journal of Controlled Release

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Sustained vaginal delivery of siRNA has been precluded by the mucosal barrier lining the vaginal tract. In contrast to prior reports, we showed that conventional lipoplexes administered intravaginally are unable to reach the vaginal epithelium under normal physiological conditions. Here we have developed a novel alginate scaffold system containing muco-inert PEGylated lipoplexes to provide a sustained vaginal presence of lipoplexes in vivo and to facilitate the delivery of siRNA/oligonucleotides into the vaginal epithelium. These PEGylated lipoplex-entrapped alginate scaffolds (PLAS) were fabricated using a freeze-drying method and the entrapment efficiency, release rate, and efficacy were characterized. We demonstrated that the PLAS system had an entrapment efficiency of ~50%, which released PEGylated lipoplexes gradually both in vitro and in vivo. While the presence of alginate diminished the cell uptake efficiency of PEGylated lipoplexes in vitro, as expected, we showed a six-fold increase their uptake into the vaginal epithelium compared to existing transfection systems following intravaginal administration in mice. A significant knockdown of Lamin A/C level was also observed in vaginal tissues using siLamin A/C-containing PLAS system in vivo. Overall, our results indicated the potential of the biodegradable PLAS system for the sustained delivery of siRNA/oligonucleotides to vaginal epithelium.

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“…An anti‐apoptotic role for Grb10 has been demonstrated in several other cell models (Jahn et al, 2002; Kebache et al, 2007; Hu et al, 2010). Further, Grb10 expression has been shown to be upregulated in some tumor types (Casas et al, 2003; Mirmohammadsadegh et al, 2004; Okino et al, 2005) and downregulated in others (Yu et al, 2011). Perhaps relevant to these studies, disruption of a maternally imprinted allele of Grb10 resulted in a general overgrowth of resulting mice, although the kidney was spared (Garfield et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

HuR inhibits apoptosis by amplifying Akt signaling through a positive feedback loop

Singh

Martinez

Govindaraju

et al. 2012

Journal Cellular Physiology

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Human antigen R (HuR) is a post-transcriptional regulator of gene expression that plays a key role in stabilizing mRNAs during cellular stress, leading to enhanced survival. HuR expression is tightly regulated through multiple transcription and post-transcriptional controls. Although HuR is known to stabilize a subset of mRNAs involved in cell survival, its role in the survival pathway of PI3-kinase/Akt signaling is unclear. Here, we show that in renal proximal tubule cells, HuR performs a central role in cell survival by amplifying Akt signaling in a positive feedback loop. Key to this feedback loop is HuR-mediated stabilization of mRNA encoding Grb10, an adaptor protein whose expression is critical for Akt activation. Stimulation of Akt by interaction with Grb10 then activates NF-κB, which further enhances HuR mRNA and protein expression. This feedback loop is active in unstressed cells, but its effects are increased during stress. Therefore, this study demonstrates a central role for HuR in Akt signaling and reveals a mechanism by which modest changes in HuR levels below or above normal may be amplified, potentially resulting in cell death or cellular transformation.

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Up-regulation of growth factor receptor-bound protein 10 in cervical squamous cell carcinoma

Cited by 14 publications

References 0 publications

Proproliferative function of adaptor protein GRB10 in prostate carcinoma

Proproliferative function of adaptor protein GRB10 in prostate carcinoma

Vaginal delivery of siRNA using a novel PEGylated lipoplex-entrapped alginate scaffold system

HuR inhibits apoptosis by amplifying Akt signaling through a positive feedback loop

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