Quantitative proteomics reveals the downregulation of GRB2 as a prominent node of F806-targeted cell proliferation network

Li, Liyan; Zhang, Kai; Jiang, Hong; Xie, Yang‐Min; Liao, Lian‐Di; Chen, Bin; Du, Zhifeng; Zhang, Pi‐Xian; Chen, Hong; Huang, Wei; Jia, Wei; Cao, Hongxin; Zheng, Wei; Li, En‐Min; Xu, Li‐Yan

doi:10.1016/j.jprot.2015.01.016

Cited by 15 publications

(17 citation statements)

References 32 publications

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“…Previous reports showed that F806 can downregulate expression of ITGB1 and GRB2 proteins that participate in the connection of actin fibers to plasma membrane, in ESCC cell lines [ 12 , 13 ]. Therefore, we examined whether the inhibitory effect of F806 on ESCC invasion and metastasis was correlated with alterations in F-actin rearrangement.…”

Section: Resultsmentioning

confidence: 99%

“…Our previous studies showed that F806 suppresses cancer progression; though it downregulates the protein expression of actin cytoskeleton linkers ITGB1 and GRB2 [ 12 , 13 ], proteins are involved in the formation of focal adhesions, which implies F806 can control dynamic changes of the cytoskeleton. We determined whether F806 could take part in the regulation of actin assembly and cancer metastasis by analyzing the function of F806-downregulating proteins in the above two biological processes [ 24 , 26 – 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…We determined whether F806 could take part in the regulation of actin assembly and cancer metastasis by analyzing the function of F806-downregulating proteins in the above two biological processes [ 24 , 26 – 28 ]. Nevertheless, we have previously paid close attention to the therapeutic efficacy of F806 for ESCC survival and growth [ 12 , 13 , 29 , 30 ], but its regulation for ESCC migration processes had yet to be explored. Our results firstly suggest that F806, as a potential candidate compound, suppresses ESCC migration in vitro and in vivo (Figures 1 and 2 ).…”

Section: Discussionmentioning

confidence: 99%

“…F806 (purity ≥ 98.5%) was discovered and provided by Fujian Institute of Microbiology, China [ 12 , 13 ]. Cell lines used in this study were previously described [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

“…However, it is not clear whether F806 has pharmacological functions to inhibit the invasion and metastasis of ESCC cells. F806 can downregulate expression of integrin beta 1 (ITGB1) and growth factor receptor bound protein 2 (GRB2), resulting in ESCC cell apoptosis [ 12 , 13 ]. The studies showed that ITGB1- and GRB2-assosiated signaling pathways not only take part in proliferation regulation and the induction of different signaling cascades but also extensively participate in the promotion of cancer cell migration-related processes [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

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F806 Suppresses the Invasion and Metastasis of Esophageal Squamous Cell Carcinoma via Downregulating F-Actin Assembly-Related Rho Family Proteins

Xie

Zheng

et al. 2018

BioMed Research International

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Invasion and metastasis are critical pathological and mortal processes in esophageal squamous cell carcinoma (ESCC). Novel drugs, targeting the two cancer migration stages, will augment the treatment options for ESCC therapy and improve overall survival. A novel natural macrolide F806 specifically promotes apoptosis of various ESCC cells. However, whether F806 can inhibit metastasis of ESCC cells needs further evaluation. Here, our data showed that F806 inhibits dynamic F-actin assembly and then suppresses the migration of ESCC cells in vitro and their invasion and metastasis in vivo. The correlation between cancer migration and actin cytoskeleton assembly was consistent with the ability of F806 to prevent the aggregation of Paxillin, an essential protein for focal adhesion formation through binding to the ends of actin filaments. Furthermore, F806 downregulated the expression and activity of the Rho family proteins cell division cycle 42 (CDC42), RAC family small GTPase 1 (RAC1), and RAS homolog family member A (RHOA). Taken together, these results suggest that F806 can suppress cancer invasion and metastasis via interrupting the assembly of migration components involving F-actin.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…F806 (purity ≥ 98.5%) was discovered and provided by Fujian Institute of Microbiology, China [ 12 , 13 ]. Cell lines used in this study were previously described [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

F806 Suppresses the Invasion and Metastasis of Esophageal Squamous Cell Carcinoma via Downregulating F-Actin Assembly-Related Rho Family Proteins

Xie

Zheng

et al. 2018

BioMed Research International

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RAC1 inhibition reverses cisplatin resistance in esophageal squamous cell carcinoma and induces downregulation of glycolytic enzymes

Zeng

Zheng

et al. 2019

Molecular Oncology

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Development of chemoresistance remains a major challenge in treating esophageal squamous cell carcinoma (ESCC) patients despite treatment advances. However, the role of RAC1 in chemoresistance of ESCC and the underlying mechanisms remain largely unknown. In this study, we found that higher levels of RAC1 expression were associated with poorer prognosis in ESCC patients. Enhanced RAC1 expression increased cell proliferation, migration, and chemoresistance in vitro . Combination therapy using RAC1 inhibitor EHop‐016 and cisplatin significantly promoted cell viability inhibition, G2/M phase cycle arrest, and apoptosis when compared to each monotherapy. Mechanistically, glycolysis was significantly downregulated in the RAC1 inhibitor monotherapy group and the combination group via inhibiting AKT/FOXO3a signaling when compared to the control group. Moreover, the silencing of RAC1 inhibited AKT/FOXO3a signaling and cell glycolysis while the upregulation of RAC1 produced an opposite effect. In murine xenograft models, the tumor volume and the expression of glycolytic enzymes were significantly reduced in combination therapy when compared to each monotherapy group. Overall, our study demonstrates that targeting RAC1 with an inhibitor overcomes cisplatin resistance in ESCC by suppressing glycolytic enzymes, which provides a promising strategy for treatment of ESCC in clinical practice.

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α-Lipoic acid inhibits human lung cancer cell proliferation through Grb2-mediated EGFR downregulation

Yang

Wen

et al. 2017

Biochemical and Biophysical Research Communications

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Quantitative proteomics reveals the downregulation of GRB2 as a prominent node of F806-targeted cell proliferation network

Cited by 15 publications

References 32 publications

F806 Suppresses the Invasion and Metastasis of Esophageal Squamous Cell Carcinoma via Downregulating F-Actin Assembly-Related Rho Family Proteins

F806 Suppresses the Invasion and Metastasis of Esophageal Squamous Cell Carcinoma via Downregulating F-Actin Assembly-Related Rho Family Proteins

RAC1 inhibition reverses cisplatin resistance in esophageal squamous cell carcinoma and induces downregulation of glycolytic enzymes

α-Lipoic acid inhibits human lung cancer cell proliferation through Grb2-mediated EGFR downregulation

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