title: Simultaneous knockdown of uPA and MMP9 can reduce breast cancer progression by increasing cell-cell adhesion and modulating EMT genes.
abstract: In cancer progression, proteolytic enzymes like serine proteases and metalloproteinases degrade the basement membrane enabling the tumor cells to invade the adjacent tissues. Thus, invasion and metastasis are augmented by these enzymes. Simultaneous silencing of uPA and MMP9 in breast cancer cells decreased the wound healing, migratory, invasive and adhesive capacity of the cells. After simultaneous down regulation, cells were seen to be arrested in the cell cycle. There was a remarkable increase in the expression of cell to cell adhesion molecule E-cadherin, and decrease in Vimentin and Snail expression. In addition, there was a significant decrease in the expression of the stem cell marker Oct-4. In the breast tumor samples it has been observed that, tumors, expressing higher level of uPA and MMP9, express less amount of E-cadherin. It has also been observed that few tumors also show, Vimentin positive in the ductal epithelial area. Thus, our model can help for checking the aggressive tumor invasion by blocking of uPA and MMP9. Our present observations also give the concept of the presence of aggressive epithelial cells with mesenchymal nature in the tumor micro-environment, altering the expression of EMT genes.
authors.affiliation: Molecular Biology and Human Genetics Laboratory, Department of Zoology, The University of Burdwan, Golapbag, Burdwan 713104, West Bengal, India.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Moirangthem
authors.affiliation: Molecular Biology and Human Genetics Laboratory, Department of Zoology, The University of Burdwan, Golapbag, Burdwan 713104, West Bengal, India.
authors.forename: Banashree
authors.initials: B
authors.lastname: Bondhopadhyay
authors.affiliation: Department of Pathology, Burdwan Medical College and Hospital, BurdwanWest Bengal 713104, India.
authors.forename: Mala
authors.initials: M
authors.lastname: Mukherjee
authors.affiliation: Department of Pathology, Burdwan Medical College and Hospital, BurdwanWest Bengal 713104, India.
authors.forename: Arghya
authors.initials: A
authors.lastname: Bandyopadhyay
authors.affiliation: Department of Surgery, Burdwan Medical College and Hospital, BurdwanWest Bengal 713104, India.
authors.forename: Narendranath
authors.initials: N
authors.lastname: Mukherjee
authors.affiliation: Department of Pathology, Burdwan Medical College and Hospital, BurdwanWest Bengal 713104, India.
authors.forename: Karabi
authors.initials: K
authors.lastname: Konar
authors.affiliation: Department of Pathology, Burdwan Medical College and Hospital, BurdwanWest Bengal 713104, India.
authors.forename: Shubham
authors.initials: S
authors.lastname: Bhattacharya
authors.affiliation: Molecular Biology and Human Genetics Laboratory, Department of Zoology, The University of Burdwan, Golapbag, Burdwan 713104, West Bengal, India.
authors.forename: Anupam
authors.initials: A
authors.lastname: Basu
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002465:Cell Movement; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; D014746:Vimentin; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9