Abstract:
:The guanosine triphosphatases of the Rho and Rac subfamilies regulate protumorigenic pathways and are activated by guanine nucleotide exchange factors (Rho GEFs), which could be potential targets for anticancer therapies. We report that two Rho GEFs, Vav2 and Vav3, play synergistic roles in breast cancer by sustaining tumor growth, neoangiogenesis, and many of the steps involved in lung-specific metastasis. The involvement of Vav proteins in these processes did not correlate with Rac1 and RhoA activity or cell migration, implying the presence of additional biological programs. Microarray analyses revealed that Vav2 and Vav3 controlled a vast transcriptional program in breast cancer cells through mechanisms that were shared between the two proteins, isoform-specific or synergistic. Furthermore, the abundance of Vav-regulated transcripts was modulated by Rac1-dependent and Rac1-independent pathways. This transcriptome encoded therapeutically targetable proteins that played nonredundant roles in primary tumorigenesis and lung-specific metastasis, such as integrin-linked kinase (Ilk), the transforming growth factor-β family ligand inhibin βA, cyclooxygenase-2, and the epithelial cell adhesion molecule Tacstd2. It also contained gene signatures that predicted disease outcome in breast cancer patients. These results identify possible targets for treating breast cancer and lung metastases and provide a potential diagnostic tool for clinical use.
journal_name
Sci Signaljournal_title
Science signalingauthors
Citterio C,Menacho-Márquez M,García-Escudero R,Larive RM,Barreiro O,Sánchez-Madrid F,Paramio JM,Bustelo XRdoi
10.1126/scisignal.2002962subject
Has Abstractpub_date
2012-10-02 00:00:00pages
ra71issue
244eissn
1945-0877issn
1937-9145pii
5/244/ra71journal_volume
5pub_type
杂志文章abstract::The cytokine interleukin-22 (IL-22), which is a member of the IL-10 family, is produced exclusively by immune cells and activates signal transducer and activator of transcription 3 (STAT3) in nonimmune cells, such as hepatocytes, keratinocytes, and colonic epithelial cells, to drive various processes central to tissue...
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pub_type: 评论,杂志文章,评审
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journal_title:Science signaling
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pub_type: 社论,历史文章,评审
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pub_type: 杂志文章,评审
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pub_type: 评论,杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章,评审
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pub_type: 评论,信件
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