title: The SOX11 transcription factor is a critical regulator of basal-like breast cancer growth, invasion, and basal-like gene expression.
abstract: Basal-like breast cancers (BLBCs) are aggressive breast cancers associated with poor survival. Defining the key drivers of BLBC growth will allow identification of molecules for targeted therapy. In this study, we performed a primary screen integrating multiple assays that compare transcription factor expression and activity in BLBC and non-BLBC at the RNA, DNA, and protein levels. This integrated screen identified 33 transcription factors that were elevated in BLBC in multiple assays comparing mRNA expression, DNA cis-element sequences, or protein DNA-binding activity. In a secondary screen to identify transcription factors critical for BLBC cell growth, 8 of the 33 candidate transcription factors (TFs) were found to be necessary for growth in at least two of three BLBC cell lines. Of these 8 transcription factors, SOX11 was the only transcription factor required for BLBC growth, but not for growth of non-BLBC cells. Our studies demonstrate that SOX11 is a critical regulator of multiple BLBC phenotypes, including growth, migration, invasion, and expression of signature BLBC genes. High SOX11 expression was also found to be an independent prognostic indicator of poor survival in women with breast cancer. These results identify SOX11 as a potential target for the treatment of BLBC, the most aggressive form of breast cancer.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.|Department of Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Shepherd
authors.affiliation: Department of Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Ivan P
authors.initials: IP
authors.lastname: Uray
authors.affiliation: Department of Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Abhijit
authors.initials: A
authors.lastname: Mazumdar
authors.affiliation: The Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Tsimelzon
authors.affiliation: Department of Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Savage
authors.affiliation: The Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Susan G
authors.initials: SG
authors.lastname: Hilsenbeck
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.|Department of Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Powel H
authors.initials: PH
authors.lastname: Brown
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology; D055751:SOXC Transcription Factors / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C097473:SOX11 protein, human; D055751:SOXC Transcription Factors
keywords: SOX11; basal-like breast cancer; growth; migration; transcription factor