title: LARP7 suppresses P-TEFb activity to inhibit breast cancer progression and metastasis.
abstract: 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.
authors: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
authors: Xiaodan
authors: X
authors: Ji
authors: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States School of Pharmaceutical Sciences, Xiamen University, Xiamen, China.
authors: Huasong
authors: H
authors: Lu
authors: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
authors: Qiang
authors: Q
authors: Zhou
authors: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, United States kluo@berkeley.edu.
authors: Kunxin
authors: K
authors: Luo
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D042925:Positive Transcriptional Elongation Factor B / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012342:RNA, Small Nuclear / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; C528908:Larp7 protein, human; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D012342:RNA, Small Nuclear; D012097:Repressor Proteins; D012261:Ribonucleoproteins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; C082078:mesenchyme fork head 1 protein; D042925:Positive Transcriptional Elongation Factor B
keywords: 7SK snRNA; EMT; LARP7; P-TEFb; breast cancer; super elongation complex