Limits...
Flotillin-2 promotes nasopharyngeal carcinoma metastasis and is necessary for the epithelial-mesenchymal transition induced by transforming growth factor-β.

Zhao L, Lin L, Pan C, Shi M, Liao Y, Bin J, Liao W - Oncotarget (2015)

Bottom Line: In this study, we found that Flot2 expression level positively correlated with the cancer stage in NPC tissues.In NPC cells, silencing Flot2 reversed the metastatic effect induced by TGF-β.Moreover, TGF-β-induced Src phosphorylation was significantly inhibited by Flot2 knocking down.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou Guangdong 510515, China.

ABSTRACT
Transforming growth factor-β (TGF-β) promotes cancer metastasis via the epithelial-mesenchymal transition (EMT) but the underlying mechanisms in nasopharyngeal carcinoma (NPC) remain unclear. Flotillin-2 (Flot2), a specialized lipid raft domain in cellular membrane, was reported to promote cancer metastasis. Recently, in neuropathy, it was also suggested that Flot2 was involved in Src activation, which is known as the downstream signal of TGF-β. Therefore, we intended to find out the relationship between Flot2 and TGF-β in the process of nasopharyngeal carcinoma (NPC) metastasis. In this study, we found that Flot2 expression level positively correlated with the cancer stage in NPC tissues. Elevated Flot2 in tumor tissue was an independent prognostic marker, and higher Flot2 expression level showed shorter overall survival time in 181 NPC patients. In NPC cells, silencing Flot2 reversed the metastatic effect induced by TGF-β. Moreover, TGF-β-induced Src phosphorylation was significantly inhibited by Flot2 knocking down. As the consequence of Flot2 inhibition, the expression of the epithelial biomarker E-cadherin was upregulated, while the mesenchymal marker vimentin and signaling transducer β-catenin was suppressed. In conclusions, Flot2 is an indispensable member for TGF-β signaling, which is essential for the EMT process in NPC metastasis. Suppressing Flot2 may be a novel way against TGF-β-induced EMT.

No MeSH data available.


Related in: MedlinePlus

Summarizing diagram of this studySummarizing diagram of this study. Flot2 is indispensable for Src phosphorylation in TGF-β signaling. Silencing Flot2 reverses the TGF-β-induced EMT in NPC cells by suppressing Src activation. By this, E-cadherin expression is upregulated and vimentin and β-catenin expressions are downregulated. These findings answer our clinical observations why Flot2 elevation is associated with more lymphatic as well as distant metastasis, and consequently lead to adverse survival outcomes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4496397&req=5

Figure 7: Summarizing diagram of this studySummarizing diagram of this study. Flot2 is indispensable for Src phosphorylation in TGF-β signaling. Silencing Flot2 reverses the TGF-β-induced EMT in NPC cells by suppressing Src activation. By this, E-cadherin expression is upregulated and vimentin and β-catenin expressions are downregulated. These findings answer our clinical observations why Flot2 elevation is associated with more lymphatic as well as distant metastasis, and consequently lead to adverse survival outcomes.

Mentions: In conclusion, we discovered the clinical significance of Flot2 in promoting NPC metastasis and consequently leading to adverse prognosis. Then, our experiment showed that TGF-β-induced Src activation and promotes EMT in NPC cells. In cooperation with Src phosphorylation, Flot2 was an indispensable member for TGF-β signaling. Taken these together, our data suggest that suppressing Flot2 may be a novel way against TGF-β-induced EMT in NPC (Figure 7).


Flotillin-2 promotes nasopharyngeal carcinoma metastasis and is necessary for the epithelial-mesenchymal transition induced by transforming growth factor-β.

Zhao L, Lin L, Pan C, Shi M, Liao Y, Bin J, Liao W - Oncotarget (2015)

Summarizing diagram of this studySummarizing diagram of this study. Flot2 is indispensable for Src phosphorylation in TGF-β signaling. Silencing Flot2 reverses the TGF-β-induced EMT in NPC cells by suppressing Src activation. By this, E-cadherin expression is upregulated and vimentin and β-catenin expressions are downregulated. These findings answer our clinical observations why Flot2 elevation is associated with more lymphatic as well as distant metastasis, and consequently lead to adverse survival outcomes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496397&req=5

Figure 7: Summarizing diagram of this studySummarizing diagram of this study. Flot2 is indispensable for Src phosphorylation in TGF-β signaling. Silencing Flot2 reverses the TGF-β-induced EMT in NPC cells by suppressing Src activation. By this, E-cadherin expression is upregulated and vimentin and β-catenin expressions are downregulated. These findings answer our clinical observations why Flot2 elevation is associated with more lymphatic as well as distant metastasis, and consequently lead to adverse survival outcomes.
Mentions: In conclusion, we discovered the clinical significance of Flot2 in promoting NPC metastasis and consequently leading to adverse prognosis. Then, our experiment showed that TGF-β-induced Src activation and promotes EMT in NPC cells. In cooperation with Src phosphorylation, Flot2 was an indispensable member for TGF-β signaling. Taken these together, our data suggest that suppressing Flot2 may be a novel way against TGF-β-induced EMT in NPC (Figure 7).

Bottom Line: In this study, we found that Flot2 expression level positively correlated with the cancer stage in NPC tissues.In NPC cells, silencing Flot2 reversed the metastatic effect induced by TGF-β.Moreover, TGF-β-induced Src phosphorylation was significantly inhibited by Flot2 knocking down.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou Guangdong 510515, China.

ABSTRACT
Transforming growth factor-β (TGF-β) promotes cancer metastasis via the epithelial-mesenchymal transition (EMT) but the underlying mechanisms in nasopharyngeal carcinoma (NPC) remain unclear. Flotillin-2 (Flot2), a specialized lipid raft domain in cellular membrane, was reported to promote cancer metastasis. Recently, in neuropathy, it was also suggested that Flot2 was involved in Src activation, which is known as the downstream signal of TGF-β. Therefore, we intended to find out the relationship between Flot2 and TGF-β in the process of nasopharyngeal carcinoma (NPC) metastasis. In this study, we found that Flot2 expression level positively correlated with the cancer stage in NPC tissues. Elevated Flot2 in tumor tissue was an independent prognostic marker, and higher Flot2 expression level showed shorter overall survival time in 181 NPC patients. In NPC cells, silencing Flot2 reversed the metastatic effect induced by TGF-β. Moreover, TGF-β-induced Src phosphorylation was significantly inhibited by Flot2 knocking down. As the consequence of Flot2 inhibition, the expression of the epithelial biomarker E-cadherin was upregulated, while the mesenchymal marker vimentin and signaling transducer β-catenin was suppressed. In conclusions, Flot2 is an indispensable member for TGF-β signaling, which is essential for the EMT process in NPC metastasis. Suppressing Flot2 may be a novel way against TGF-β-induced EMT.

No MeSH data available.


Related in: MedlinePlus