title: Profilin1 facilitates staurosporine-triggered apoptosis by stabilizing the integrin β1-actin complex in breast cancer cells.
abstract: Profilin1 (Pfn1) functions as a tumour suppressor against malignant phenotypes of cancer cells. A minimum level of Pfn1 is critical for the differentiation of human epithelial cells, and its lower expression correlates with the tumourigenesis of breast cancer cells and tissues. However, the molecular mechanisms underlying its anti-tumour action remain largely unknown. 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. Pfn1 overexpression could also up-regulate the expression of integrin α5β1, which has been shown to inhibit the transformed phenotype of cancer cells. Furthermore, the Pfn1-facilitated apoptosis induced by staurosporine was blocked in cells attached to a supplementary fibronectin substrate, which serves as a ligand of integrin α5β1. 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. Moreover, Pfn1 that primarily functions to promote local superstructure formation involving actin filaments and integrin β1 may contribute to its promotion on 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Wantong
authors.initials: W
authors.lastname: Yao
authors.forename: Xianjun
authors.initials: X
authors.lastname: Yu
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: Fang
authors.forename: Peng
authors.initials: P
authors.lastname: Yin
authors.forename: Chao
authors.initials: C
authors.lastname: Zhao
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Liying
authors.initials: L
authors.lastname: Wang
authors.forename: Zengxia
authors.initials: Z
authors.lastname: Li
authors.forename: Xiliang
authors.initials: X
authors.lastname: Zha
mesh_terms: D000199:Actins / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D018613:Microscopy, Confocal; D051304:Profilins / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D019311:Staurosporine / Q000494:pharmacology*
chemical_list: D000199:Actins; D004791:Enzyme Inhibitors; D019012:Integrin beta1; C495738:PFN1 protein, human; D051304:Profilins; D019311:Staurosporine