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Profilin1 facilitates staurosporine-triggered apoptosis by stabilizing the integrin β1-actin complex in breast cancer cells.

Yao W, Yu X, Fang Z, Yin P, Zhao C, Li N, Wang L, Li Z, Zha X - J. Cell. Mol. Med. (2012)

Bottom Line: In this study, we found that stable expression of ectopic Pfn1 sensitized the breast cancer cell line MDA-MB-468 to apoptosis induced by staurosporine, a widely used natural apoptosis-inducing agent.These results suggest that the insufficient fibronectin caused by the integrin α5β1 up-regulation might activate a signalling pathway leading to an increase of cellular apoptosis.Our study indicated a previously uncharacterized role of Pfn1 in mediating staurosporine-inducing apoptosis in breast cancer cells via up-regulating integrin α5β1, and suggested a new target for breast cancer therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China.

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Related in: MedlinePlus

Schematic diagram for the role of Pfn1 under STS condition. Pfn1 overexpression increases actin filament assembly and then enhances the binding among Pfn1, actin and integrin β1, which form a more stable complex on the plasma membrane. The co-administration of them in such cells leads to retention of integrin β1 on the membrane, thus inhibiting its degradation by proteosome. The up-regulated integrin β1 involves in apoptotic susceptivity facilitated by Pfn1 overexpression. The increased integrin α5β1 receptor by Pfn1 overexpression is excess to fibronectin as an extracellular ligand. Accordingly, the ligation state of the integrin α5β1 molecule with FN influenced by ectopic Pfn1 accounts for the cell apoptotic sensitivity under STS treatment.
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fig07: Schematic diagram for the role of Pfn1 under STS condition. Pfn1 overexpression increases actin filament assembly and then enhances the binding among Pfn1, actin and integrin β1, which form a more stable complex on the plasma membrane. The co-administration of them in such cells leads to retention of integrin β1 on the membrane, thus inhibiting its degradation by proteosome. The up-regulated integrin β1 involves in apoptotic susceptivity facilitated by Pfn1 overexpression. The increased integrin α5β1 receptor by Pfn1 overexpression is excess to fibronectin as an extracellular ligand. Accordingly, the ligation state of the integrin α5β1 molecule with FN influenced by ectopic Pfn1 accounts for the cell apoptotic sensitivity under STS treatment.

Mentions: In conclusion, this study have clearly demonstrated how Pfn1 facilitates the STS-induced apoptosis by integrin and actin complex (Fig. 7) and provided new insight into the still ill-defined role of Pfn1 in the control of breast cancer cells responsiveness to chemotherapy. The use of Pfn1 and STS may be an important clinical consideration in treating breast cancer harbouring low integrin expression. The combination of Pfn1 and STS with clinically relevant medications deserves further investigations in vitro and in vivo, in view of the fact that there is still ongoing debate concerning the relevant mechanisms.


Profilin1 facilitates staurosporine-triggered apoptosis by stabilizing the integrin β1-actin complex in breast cancer cells.

Yao W, Yu X, Fang Z, Yin P, Zhao C, Li N, Wang L, Li Z, Zha X - J. Cell. Mol. Med. (2012)

Schematic diagram for the role of Pfn1 under STS condition. Pfn1 overexpression increases actin filament assembly and then enhances the binding among Pfn1, actin and integrin β1, which form a more stable complex on the plasma membrane. The co-administration of them in such cells leads to retention of integrin β1 on the membrane, thus inhibiting its degradation by proteosome. The up-regulated integrin β1 involves in apoptotic susceptivity facilitated by Pfn1 overexpression. The increased integrin α5β1 receptor by Pfn1 overexpression is excess to fibronectin as an extracellular ligand. Accordingly, the ligation state of the integrin α5β1 molecule with FN influenced by ectopic Pfn1 accounts for the cell apoptotic sensitivity under STS treatment.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3822851&req=5

fig07: Schematic diagram for the role of Pfn1 under STS condition. Pfn1 overexpression increases actin filament assembly and then enhances the binding among Pfn1, actin and integrin β1, which form a more stable complex on the plasma membrane. The co-administration of them in such cells leads to retention of integrin β1 on the membrane, thus inhibiting its degradation by proteosome. The up-regulated integrin β1 involves in apoptotic susceptivity facilitated by Pfn1 overexpression. The increased integrin α5β1 receptor by Pfn1 overexpression is excess to fibronectin as an extracellular ligand. Accordingly, the ligation state of the integrin α5β1 molecule with FN influenced by ectopic Pfn1 accounts for the cell apoptotic sensitivity under STS treatment.
Mentions: In conclusion, this study have clearly demonstrated how Pfn1 facilitates the STS-induced apoptosis by integrin and actin complex (Fig. 7) and provided new insight into the still ill-defined role of Pfn1 in the control of breast cancer cells responsiveness to chemotherapy. The use of Pfn1 and STS may be an important clinical consideration in treating breast cancer harbouring low integrin expression. The combination of Pfn1 and STS with clinically relevant medications deserves further investigations in vitro and in vivo, in view of the fact that there is still ongoing debate concerning the relevant mechanisms.

Bottom Line: In this study, we found that stable expression of ectopic Pfn1 sensitized the breast cancer cell line MDA-MB-468 to apoptosis induced by staurosporine, a widely used natural apoptosis-inducing agent.These results suggest that the insufficient fibronectin caused by the integrin α5β1 up-regulation might activate a signalling pathway leading to an increase of cellular apoptosis.Our study indicated a previously uncharacterized role of Pfn1 in mediating staurosporine-inducing apoptosis in breast cancer cells via up-regulating integrin α5β1, and suggested a new target for breast cancer therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China.

Show MeSH
Related in: MedlinePlus