التفاصيل البيبلوغرافية
| العنوان: |
FSIP1 binds HER2 directly to regulate breast cancer growth and invasiveness. |
| المؤلفون: |
Tong Liu1, New, Maria I.2, Hao Zhang3, Jie Yang3, Xunyan Ou3, Yining Wang3, Tony Yuen3, Caigang Liu3, Li Sun3, Peng Liu3, Gupta, Animesh3, Abu-Amer, Wahid3, Zaidi, Mone3, Danyu Zhao3, Meisi Yan3, Zaidi, Neeha3, Izadmehr, Sudeh3, Minna Luo3, Xuefeng Bai3, Yan Wang3 |
| المصدر: |
Proceedings of the National Academy of Sciences of the United States of America. 7/18/2017, Vol. 114 Issue 29, p7683-7688. 6p. |
| مصطلحات موضوعية: |
*BREAST cancer treatment, *HER2 protein, *SPERMATOGENESIS, *GENE ontology, *GENE expression |
| مستخلص: |
Fibrous sheath interacting protein 1 (FSIP1), a spermatogenesisrelated testicular antigen, is expressed in abundance in breast cancers, particularly in those overexpressing human epidermal growth factor receptor 2 (HER2); however, little is known about its role in regulating the growth and metastasis of breast cancer cells. We and others have shown previously that FSIP1 expression in breast cancer correlates positively with HER2-positivity, recurrence, and metastases and negatively with survival. Here, using coimmunoprecipitation and microscale thermophoresis, we find that FSIP1 binds to the intracellular domain of HER2 directly. We further show that shRNA-induced FSIP1 knockdown in SKBR3 and MCF-7 breast cancer cells inhibits proliferation, stimulates apoptosis, attenuates epithelial-mesenchymal transition, and impairs migration and invasiveness. Consistent with reduced proliferation and enhanced apoptosis, xenotransplantation of SKBR3 cells stably transfected with sh-FSIP1 into nu/nu mice results in reduced tumor volumes compared with sh-NC transplants. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) mapping using sh-FSIP1 gene signature yielded associations with extracellular matrix protein pathways, and a reduction in SNAI2 protein expression was confirmed onWestern blot analysis. Complementarily, interrogation of the Connectivity Map using the same gene signature yielded, as top hits, chemicals known to inhibit epithelial-mesenchymal transition, including rapamycin, 17-N-allylamino-17-demethoxygeldanamycin, and LY294002. These compounds phenocopy the effects of sh-FSIP1 on SKBR3 cell viability. Thus, FSIP1 suppression limits oncogenesis and invasiveness in breast cancer cells and, considering its absence in most other tissues, including normal breast, may become a potential target for breast cancer therapy. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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