title: TGF-β-Smad2 dependent activation of CDC 25A plays an important role in cell proliferation through NFAT activation in metastatic breast cancer cells.
abstract: In late stages of cancer, TGF-β promotes the metastasis process by enhancing the invasiveness of cancer cells and inducing the epithelial-to-mesenchymal transition (EMT), a process that is concomitantly associated with breast cancer metastasis. Metastasis comprises of multiple steps with the regulation of complex network of signaling. Metastasis is associated with both the EMT and cell proliferation, but yet it has not been clearly distinguished how the balance between the cell proliferation and EMT is maintained together. Recently, it has been accounted that a transcription factor, NFAT has an important role for switching tumor suppressive to progressive effect of TGF-β and NFAT has a role in TGF-β mediated EMT by regulating N-cadherin. CDC 25A phosphatase, an important cell cycle regulator is overexpressed in breast cancer. Our results demonstrate that TGF-β regulating the CDC 25A in a Smad2 dependent way, translocates NFAT to nucleus and NFAT in co-operation with Smad2 promotes the tumor progression by upregulating the CDK2, CDK4, and cyclin E. This result signifies that TGF-β by regulating NFAT in different ways maintains the balance between EMT and cell proliferation mechanism concurrently during the late stage of breast cancer.
authors.affiliation: Immunology Lab, Department of Zoology, University of Calcutta, Kolkata, 700019 West Bengal, India; Department of Environmental Science, University of Kalyani, West Bengal 741235, India.
authors.forename: Suman
authors.initials: S
authors.lastname: Sengupta
authors.affiliation: Immunology Lab, Department of Zoology, University of Calcutta, Kolkata, 700019 West Bengal, India.
authors.forename: Samir
authors.initials: S
authors.lastname: Jana
authors.affiliation: Immunology Lab, Department of Zoology, University of Calcutta, Kolkata, 700019 West Bengal, India. Electronic address: arindam19@yahoo.com.
authors.forename: Arindam
authors.initials: A
authors.lastname: Bhattacharyya
mesh_terms: D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D015820:Cadherins; D019927:Cyclin E; D050778:NFATC Transcription Factors; D034741:RNA, Small Interfering; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; D019938:Cyclin D1; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases
keywords: CDC 25A; Cell proliferation; EMT; NFAT; Smad2; TGF-β; epithelial to mesenchymal transition; nuclear factor of activated T-cells; transforming growth factor-β