title: ERK2-ZEB1-miR-101-1 axis contributes to epithelial-mesenchymal transition and cell migration in cancer.
abstract: Regulation of metastasis continues to remain enigmatic despite our improved understanding of cancer. Identification of microRNAs associated with metastasis in the recent past has provided a new hope. Here, we show how microRNA-101 (miR-101) regulates two independent processes of cellular metastasis by targeting pro-metastatic upstream regulatory transcription factors, ZEB1 and ZEB2, and downstream effector-actin modulators, RHOA and RAC1, providing a single target for therapeutic intervention. Further, we depict how down-regulation of miR-101 by extracellular signal-regulated kinase-2 (ERK2) is vital for MAP kinase pathway induced cellular migration and mesenchymal transition. Importantly, EKR2 induced expression of ZEB1 seems essential for down-regulation of miR-101-1 and induction of EMT. Given the role of EMT in metastasis, we also observe a significant correlation between miR-101 expression and lymph node metastasis; and identify the ERK2-ZEB1-miR-101-1 pathway active in breast cancer tissues, with an apparent clinicopathological implication.
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi, Delhi 110067, India.
authors.forename: Kailash
authors.initials: K
authors.lastname: Chandra Mangalhara
authors.affiliation: School of Biotechnology, Jawaharlal Nehru University, New Delhi, Delhi 110067, India.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Manvati
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi, Delhi 110067, India.
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Saini
authors.affiliation: School of Biotechnology, Jawaharlal Nehru University, New Delhi, Delhi 110067, India.
authors.forename: Kalaiarasan
authors.initials: K
authors.lastname: Ponnusamy
authors.affiliation: Department of Endocrine & Breast Surgery, Sanjay Gandhi Post-Graduate Institute of Medical Sciences (SGPGIMS), Lucknow 226014, India.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Agarwal
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi, Delhi 110067, India.
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Abraham
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi, Delhi 110067, India. Electronic address: bamezai@hotmail.com.
authors.forename: Rameshwar N K
authors.initials: RNK
authors.lastname: Bamezai
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D014162:Transfection
chemical_list: D035683:MicroRNAs; D019950:Mitogen-Activated Protein Kinase 1
keywords: Breast cancer; Cytoskeleton; EMT-TFs; Epidermal growth factor (EGF); miR-101; microRNA