TY - JOUR
T1 - Vimentin is at the heart of epithelial mesenchymal transition (Emt) mediated metastasis
AU - Usman, Saima
AU - Waseem, Naushin H.
AU - Nguyen, Thuan Khanh Ngoc
AU - Mohsin, Sahar
AU - Jamal, Ahmad
AU - Teh, Muy Teck
AU - Waseem, Ahmad
N1 - Funding Information:
The authors would like to acknowledge the Higher Education Commission (HEC), Pakistan, the King Abdul Aziz University, Kingdom of Saudi Arabia for providing Ph.D. studentships to (S.U.) and (A.J.), respectively, The Barts Charity for the Dental Centenary Ph.D. studentship to (N.N.) and The Rosetrees Trust for financial support (M312-F1 to AW). The authors also thank the Institute of Dentistry, Barts and the London Queen Mary School of Medicine and Dentistry for waiv-ing the tuition fee that allowed S.U. to register for the PhD programme.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/10/1
Y1 - 2021/10/1
N2 - Epithelial-mesenchymal transition (EMT) is a reversible plethora of molecular events where epithelial cells gain the phenotype of mesenchymal cells to invade the surrounding tissues. EMT is a physiological event during embryogenesis (type I) but also happens during fibrosis (type II) and cancer metastasis (type III). It is a multifaceted phenomenon governed by the activation of genes associated with cell migration, extracellular matrix degradation, DNA repair, and angiogen-esis. The cancer cells employ EMT to acquire the ability to migrate, resist therapeutic agents and escape immunity. One of the key biomarkers of EMT is vimentin, a type III intermediate filament that is normally expressed in mesenchymal cells but is upregulated during cancer metastasis. This review highlights the pivotal role of vimentin in the key events during EMT and explains its role as a downstream as well as an upstream regulator in this highly complex process. This review also highlights the areas that require further research in exploring the role of vimentin in EMT. As a cytoskeletal protein, vimentin filaments support mechanical integrity of the migratory machinery, generation of directional force, focal adhesion modulation and extracellular attachment. As a visco-elastic scaffold, it gives stress-bearing ability and flexible support to the cell and its organelles. How-ever, during EMT it modulates genes for EMT inducers such as Snail, Slug, Twist and ZEB1/2, as well as the key epigenetic factors. In addition, it suppresses cellular differentiation and upregulates their pluripotent potential by inducing genes associated with self-renewability, thus increasing the stemness of cancer stem cells, facilitating the tumour spread and making them more resistant to treatments. Several missense and frameshift mutations reported in vimentin in human cancers may also contribute towards the metastatic spread. Therefore, we propose that vimentin should be a therapeutic target using molecular technologies that will curb cancer growth and spread with re-duced mortality and morbidity.
AB - Epithelial-mesenchymal transition (EMT) is a reversible plethora of molecular events where epithelial cells gain the phenotype of mesenchymal cells to invade the surrounding tissues. EMT is a physiological event during embryogenesis (type I) but also happens during fibrosis (type II) and cancer metastasis (type III). It is a multifaceted phenomenon governed by the activation of genes associated with cell migration, extracellular matrix degradation, DNA repair, and angiogen-esis. The cancer cells employ EMT to acquire the ability to migrate, resist therapeutic agents and escape immunity. One of the key biomarkers of EMT is vimentin, a type III intermediate filament that is normally expressed in mesenchymal cells but is upregulated during cancer metastasis. This review highlights the pivotal role of vimentin in the key events during EMT and explains its role as a downstream as well as an upstream regulator in this highly complex process. This review also highlights the areas that require further research in exploring the role of vimentin in EMT. As a cytoskeletal protein, vimentin filaments support mechanical integrity of the migratory machinery, generation of directional force, focal adhesion modulation and extracellular attachment. As a visco-elastic scaffold, it gives stress-bearing ability and flexible support to the cell and its organelles. How-ever, during EMT it modulates genes for EMT inducers such as Snail, Slug, Twist and ZEB1/2, as well as the key epigenetic factors. In addition, it suppresses cellular differentiation and upregulates their pluripotent potential by inducing genes associated with self-renewability, thus increasing the stemness of cancer stem cells, facilitating the tumour spread and making them more resistant to treatments. Several missense and frameshift mutations reported in vimentin in human cancers may also contribute towards the metastatic spread. Therefore, we propose that vimentin should be a therapeutic target using molecular technologies that will curb cancer growth and spread with re-duced mortality and morbidity.
KW - Amoeboid movement
KW - Cancer invasion
KW - Cancer stem cells
KW - Epithelial tu-mours
KW - Mesenchymal epithelial transition
UR - http://www.scopus.com/inward/record.url?scp=85116248319&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85116248319&partnerID=8YFLogxK
U2 - 10.3390/cancers13194985
DO - 10.3390/cancers13194985
M3 - Review article
AN - SCOPUS:85116248319
SN - 2072-6694
VL - 13
JO - Cancers
JF - Cancers
IS - 19
M1 - 4985
ER -