Simultaneous knockdown of uPA and MMP9 can reduce breast cancer progression by increasing cell-cell adhesion and modulating EMT genes

Scientific Reports
Anuradha MoirangthemAnupam Basu

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.

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Citations

Sep 21, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Hao WangYulan Ruan
Apr 24, 2019·Bioscience, Biotechnology, and Biochemistry·Ming-Jie HsuJing-Gung Chung
May 9, 2019·Cancers·Nur Izyani KamaruzmanEzharul Hoque Chowdhury
May 4, 2018·Biomedit︠s︡inskai︠a︡ khimii︠a︡·N V YunusovaI V Kondakova
Jan 3, 2020·Molecular Medicine Reports·Yongjun ChenWensheng Xu
Jun 24, 2017·Mediators of Inflammation·Jakub Kryczka, Joanna Boncela
Mar 20, 2018·British Journal of Cancer·Marieke HogervorstAbdoelwaheb El Ghalbzouri
Jul 20, 2017·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Juan F SantibanezJelena Krstić
Nov 1, 2020·Immunity, Inflammation and Disease·Fanqin BuJun Huang
Apr 4, 2021·International Journal of Molecular Sciences·Preston CareyM Sharon Stack
Mar 9, 2021·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Anuka SharmaShalmoli Bhattacharyya
Aug 19, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Fatemeh Hashemi-NiasariSoudabeh Fallah

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Methods Mentioned

BETA
MDA
transfection
PCR
Fluorescence

Software Mentioned

Image J
ImageJ
BD FACSuite

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