Up-regulation of prohibitin 1 is involved in the proliferation and migration of liver cancer cells

Xu, Zhibin; Wu, Jinhong; Zha, Xiliang

doi:10.1007/s11427-010-4130-1

Cited by 17 publications

(10 citation statements)

References 21 publications

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“…We also report the identification of 85 proteins differentially modulated by SGK1, some of which are related to RAN and RANBP1 ( Supplementary Figure S6 ). SGK1 inhibition results in down-regulation of RHOA [ 41 , 42 ], PAK2 [ 43 ]and PHB [ 44 ], all of which are involved in progression through G2/M. These proteins are also over-expressed in conditions associated with liver metastasis, mitotic instability and drug resistance [ 42 – 44 ].…”

Section: Discussionmentioning

confidence: 99%

“…SGK1 inhibition results in down-regulation of RHOA [ 41 , 42 ], PAK2 [ 43 ]and PHB [ 44 ], all of which are involved in progression through G2/M. These proteins are also over-expressed in conditions associated with liver metastasis, mitotic instability and drug resistance [ 42 – 44 ]. On the other hand, ST-13 [ 45 , 46 ] and MLC [ 47 ], two down-regulated proteins in HCC, appear to be over-expressed upon SI113-dependent SGK1 inhibition.…”

Section: Discussionmentioning

confidence: 99%

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Preclinical model in HCC: the SGK1 kinase inhibitor SI113 blocks tumor progressionin vitroandin vivoand synergizes with radiotherapy

et al. 2015

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The SGK1 kinase is pivotal in signal transduction pathways operating in cell transformation and tumor progression. Here, we characterize in depth a novel potent and selective pyrazolo[3,4-d]pyrimidine-based SGK1 inhibitor. This compound, named SI113, active in vitro in the sub-micromolar range, inhibits SGK1-dependent signaling in cell lines in a dose- and time-dependent manner. We recently showed that SI113 slows down tumor growth and induces cell death in colon carcinoma cells, when used in monotherapy or in combination with paclitaxel. We now demonstrate for the first time that SI113 inhibits tumour growth in hepatocarcinoma models in vitro and in vivo. SI113-dependent tumor inhibition is dose- and time-dependent. In vitro and in vivo SI113-dependent SGK1 inhibition determined a dramatic increase in apotosis/necrosis, inhibited cell proliferation and altered the cell cycle profile of treated cells. Proteome-wide biochemical studies confirmed that SI113 down-regulates the abundance of proteins downstream of SGK1 with established roles in neoplastic transformation, e.g. MDM2, NDRG1 and RAN network members. Consistent with knock-down and over-expressing cellular models for SGK1, SI113 potentiated and synergized with radiotherapy in tumor killing. No short-term toxicity was observed in treated animals during in vivo SI113 administration. These data show that direct SGK1 inhibition can be effective in hepatic cancer therapy, either alone or in combination with radiotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Preclinical model in HCC: the SGK1 kinase inhibitor SI113 blocks tumor progressionin vitroandin vivoand synergizes with radiotherapy

et al. 2015

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“…However, there is emerging evidence that prohibitin as a protein is required for cell proliferation and adhesion [47] . This protein is also known for activating the Raf-MEK-ERK signaling pathway and inducing cell migration [36] , [48] . Another protein found to be upregulated after treatment with cyclopamine and tamoxifen is keratin 8.…”

Section: Discussionmentioning

confidence: 99%

Combination of Cyclopamine and Tamoxifen Promotes Survival and Migration of MCF-7 Breast Cancer Cells – Interaction of Hedgehog-Gli and Estrogen Receptor Signaling Pathways

et al. 2014

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Hedgehog-Gli (Hh-Gli) signaling pathway is one of the new molecular targets found upregulated in breast tumors. Estrogen receptor alpha (ERα) signaling has a key role in the development of hormone-dependent breast cancer. We aimed to investigate the effects of inhibiting both pathways simultaneously on breast cancer cell survival and the potential interactions between these two signaling pathways. ER-positive MCF-7 cells show decreased viability after treatment with cyclopamine, a Hh-Gli pathway inhibitor, as well as after tamoxifen (an ERα inhibitor) treatment. Simultaneous treatment with cyclopamine and tamoxifen on the other hand, causes short-term survival of cells, and increased migration. We found upregulated Hh-Gli signaling under these conditions and protein profiling revealed increased expression of proteins involved in cell proliferation and migration. Therefore, even though Hh-Gli signaling seems to be a good potential target for breast cancer therapy, caution must be advised, especially when combining therapies. In addition, we also show a potential direct interaction between the Shh protein and ERα in MCF-7 cells. Our data suggest that the Shh protein is able to activate ERα independently of the canonical Hh-Gli signaling pathway. Therefore, this may present an additional boost for ER-positive cells that express Shh, even in the absence of estrogen.

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“…Higher levels of PHB expression were found in regenerating liver cells, chemically-induced carcinoma, hyperplastic hepatic nodules and hepatocellular carcinomas, and in cancer cells and primary tumor samples (7,22–24). The expression of PHB increases in yeast cells during diauxic shift when cells switch from non-oxidative to oxidative metabolism (7).…”

Section: Introductionmentioning

confidence: 99%

β-catenin induces expression of prohibitin gene in acute leukemic cells

et al. 2017

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Prohibitin (PHB) is a multifunctional protein conserved in eukaryotic systems and shows various expression levels in tumor cells. However, regulation of PHB is not clearly understood. Here, we focused on the regulation of PHB expression by Wnt signaling, one of dominant regulatory signals in various leukemic cells. High mRNA levels of PHB were found in half of clinical leukemia samples. PHB expression was increased by inhibition of the MAPK pathway and decreased by activation of EGF signal. Although cell proliferating signals downregulated the transcription of PHB, treatment with lithium chloride, an analog of the Wnt signal, induced PHB level in various cell types. We identified the TCF-4/LEF-1 binding motif, CATCTG, in the promoter region of PHB by site-directed mutagenesis and ChIP assay. This β-catenin-mediated activation of PHB expression was independent of c-MYC activation, a product of Wnt signaling. These data indicate that PHB is a direct target of β-catenin and the increased level of PHB in leukemia can be regulated by Wnt signaling.

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Up-regulation of prohibitin 1 is involved in the proliferation and migration of liver cancer cells

Cited by 17 publications

References 21 publications

Preclinical model in HCC: the SGK1 kinase inhibitor SI113 blocks tumor progressionin vitroandin vivoand synergizes with radiotherapy

Preclinical model in HCC: the SGK1 kinase inhibitor SI113 blocks tumor progressionin vitroandin vivoand synergizes with radiotherapy

Combination of Cyclopamine and Tamoxifen Promotes Survival and Migration of MCF-7 Breast Cancer Cells – Interaction of Hedgehog-Gli and Estrogen Receptor Signaling Pathways

β-catenin induces expression of prohibitin gene in acute leukemic cells

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