Multifaceted role of tensins in cancer
- Published
- Accepted
- Subject Areas
- Cell Biology, Molecular Biology, Oncology, Pathology
- Keywords
- tensins, Cten, cancer, extracellular matrix, focal adhesions, molecular mapping, adaptor proteins
- Copyright
- © 2019 Alfahed et al.
- Licence
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ Preprints) and either DOI or URL of the article must be cited.
- Cite this article
- 2019. Multifaceted role of tensins in cancer. PeerJ Preprints 7:e27990v1 https://doi.org/10.7287/peerj.preprints.27990v1
Abstract
Tensins are structural adaptor proteins localized at focal adhesions. Tensins can act as mechanosensors and participate in the transduction of biochemical signals from the extracellular matrix to the cytoskeleton, acting as an interface able to alter cell behavior in responses to changes in their surrounding environment. This review aims to provide a concise summary of the main functions of the four known tensins in cell and cancer biology, their homology and recently unveiled signaling mechanisms. We focus specifically on how tensin 4 (TNS4/Cten) may contribute to cancer both as an oncogene supporting metastasis and as tumour suppressor in different types of tissue. A better understanding of the cancer mechanistics involving tensins may provide the rationale for development of specific therapeutic strategies.
Author Comment
This is a preprint submission to PeerJ Preprints.
Supplemental Information
Figure 1 - Structure of members of the Tensin family and phylogenetic tree
(A) Structure of members of the Tensin family. Tensin-1, Tensin-2 and Tensin-3 contain an ABD (actin binding domain), SH2 (Src homology 2) domain and PTB (phosphotyrosine binding domain). Tensin-2 has a conserved protein kinase C region 1 that is not present in other Tensins. TNS4 has a SH2 domain and PTB domain but lacks the ABD. Among all Tensins, Nuclear localization signal (NLS) and Nuclear export signal (NES) was identified in TNS4. (B) Molecular Phylogenetic analysis of tensins by Maximum Likelihood method
Figure 2 - Phylogenetic tree of tensin 4 in domestic mammals
Molecular Phylogenetic analysis of tensin 4 in domestic mammals by Maximum Likelihood method
Figure 3 - NLS Alignment in tensins
Alignment of NLS regions in the four tensins and highlighted conserved amino acid residues.
Figure 4 - Homology for the SH2 domain in the four tensins
Homology for the SH2 domain across the four tensins. High conservation of tyrosine (Y) residues is indicated by * and low conservavtion indicated by +.
Figure 5 - TNS3 and TNS4 upregulation
TNS3 and TNS4 upregulation following EGF stimulation in colorectal cancer.
Figure 6 - TNS1-DLC1 interaction
TNS1 interaction with DLC1 and effects on RhoA.
Figure 7 - TNS4-Beta-catenin interaction
Predicted interaction between the N-terminal part of TNS4 and a grove in the armadillo structure of Beta-catenin.
Figure 8 - Network of Beta-catenin and TNS4 interactors
Network of Beta-catenin and TNS4 interactors (thebiogrid.org). EGFR (circled in red) is a common interactor for both proteins.
Supplementary Figure 1
Tensins 1-4 homology alignment and highlighted domains. ABD - Actin-binding domain; PTP - Phosphatase Tensin type; C1 - Protein kinase C conserved region; C2 - tensin type domain, SH2 - Src homology region, PTB - phosphotyrosine binding region NLS - nuclear localization signal.
Table 1 - In vitro assays of TNS4 function and TNS4 expression in clinical samples
Summary of the reported functions of TNS4 in vitro and associations between TNS4 expression in clinical samples and patient outcomes in various types of cancerous and normal tissues.