MicroRNAs and Growth Factors: An Alliance Propelling Tumor Progression.
Tumor progression requires cancer cell proliferation, migration, invasion, and attraction of blood and lymph vessels. These processes are tightly regulated by growth factors and their intracellular signaling pathways, which culminate in transcriptional programs. Hence, oncogenic mutations often capture growth factor signaling, and drugs able to intercept the underlying biochemical routes might retard cancer spread. Along with messenger RNAs, microRNAs play regulatory roles in growth factor signaling and in tumor progression. Because growth factors regulate abundance of certain microRNAs and the latter modulate the abundance of proteins necessary for growth factor signaling, the two classes of molecules form a dense web of interactions, which are dominated by a few recurring modules. We review specific examples of the alliance formed by growth factors and microRNAs and refer primarily to the epidermal growth factor (EGF) pathway. Clinical applications of the crosstalk between microRNAs and growth factors are described, including relevance to cancer therapy and to emergence of resistance to specific drugs.
Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel. meravk@tlvmc.gov.il.
Merav
M
Kedmi
Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel. aldema.sas@weizmann.ac.il.
Aldema
A
Sas-Chen
Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel. yosef.yarden@weizmann.ac.il.
Yosef
Y
Yarden
cancer therapy; carcinoma; epidermal growth factor (EGF); metastasis; network; receptor tyrosine kinase; signal transduction; transcription