TY - JOUR TI - LARP7 suppresses P-TEFb activity to inhibit breast cancer progression and metastasis AU - Ji, Xiaodan AU - Lu, Huasong AU - Zhou, Qiang AU - Luo, Kunxin A2 - Espinosa, Joaquin M VL - 3 PY - 2014 DA - 2014/07/22 SP - e02907 C1 - eLife 2014;3:e02907 DO - 10.7554/eLife.02907 UR - https://doi.org/10.7554/eLife.02907 AB - Transcriptional elongation by RNA polymerase (Pol) II is essential for gene expression during cell growth and differentiation. The positive transcription elongation factor b (P-TEFb) stimulates transcriptional elongation by phosphorylating Pol II and antagonizing negative elongation factors. A reservoir of P-TEFb is sequestered in the inactive 7SK snRNP where 7SK snRNA and the La-related protein LARP7 are required for the integrity of this complex. Here, we show that P-TEFb activity is important for the epithelial–mesenchymal transition (EMT) and breast cancer progression. Decreased levels of LARP7 and 7SK snRNA redistribute P-TEFb to the transcriptionally active super elongation complex, resulting in P-TEFb activation and increased transcription of EMT transcription factors, including Slug, FOXC2, ZEB2, and Twist1, to promote breast cancer EMT, invasion, and metastasis. Our data provide the first demonstration that the transcription elongation machinery plays a key role in promoting breast cancer progression by directly controlling the expression of upstream EMT regulators. KW - P-TEFb KW - LARP7 KW - 7SK snRNA KW - super elongation complex KW - breast cancer KW - EMT JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -