title: FOXQ1 regulates epithelial-mesenchymal transition in human cancers.
abstract: Epithelial-mesenchymal transition (EMT) in cancer cells plays a pivotal role in determining metastatic prowess, but knowledge of EMT regulation remains incomplete. In this study, we defined a critical functional role for the Forkhead transcription factor FOXQ1 in regulating EMT in breast cancer cells. FOXQ1 expression was correlated with high-grade basal-like breast cancers and was associated with poor clinical outcomes. RNAi-mediated suppression of FOXQ1 expression in highly invasive human breast cancer cells reversed EMT, reduced invasive ability, and alleviated other aggressive cancer phenotypes manifested in 3-dimensional Matrigel (BD Biosciences) culture. Conversely, enforced expression of FOXQ1 in differentiated human mammary epithelial cells (HMLER) or epithelial cancer cell lines provoked an epithelial to mesenchymal morphologic change, gain of stem cell-like properties, and acquisition of resistance to chemotherapy-induced apoptosis. Mechanistic investigations revealed that FOXQ1-induced EMT was associated with transcriptional inactivation of the epithelial regulator E-cadherin (CDH1). Our findings define a key role for FOXQ1 in regulating EMT and aggressiveness in human cancer.
authors.affiliation: Cancer Biology and Pharmacology and Information and Mathematical Science, Genome Institute of Singapore, Agency for Science, Technology and Research, Biopolis, Singapore.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Qiao
authors.forename: Xia
authors.initials: X
authors.lastname: Jiang
authors.forename: Shuet Theng
authors.initials: ST
authors.lastname: Lee
authors.forename: R K Murthy
authors.initials: RK
authors.lastname: Karuturi
authors.forename: Shing Chuan
authors.initials: SC
authors.lastname: Hooi
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D034622:RNA Interference; D014158:Transcription, Genetic
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; C484579:FOXQ1 protein, human; D051858:Forkhead Transcription Factors