DUSP10 Is a Regulator of YAP1 Activity Promoting Cell Proliferation and Colorectal Cancer Progression
Abstract
:1. Introduction
2. Results
2.1. DUSP10 Regulates Cell Proliferation of CRC Cell Lines In Vitro and In Vivo
2.2. DUSP10 Is Increased in HD and Correlates with YAP1 Expression in CRC Cell Lines
2.3. DUSP10 Interacts with YAP1 through Ser397 Residue
2.4. DUSP10 Regulates the Hippo Pathway in Drosophila
2.5. DUSP10 Is Increased in CRC Patient Samples
2.6. Nuclear DUSP10 Expression Correlates with Bad Prognosis in CRC Patients
3. Discussion
4. Materials and Methods
4.1. Cell Lines and Cell Culture
4.2. Transient Expression Constructs
4.3. Stable Expression Constructs
4.4. Cell Proliferation Assays
4.5. Cell Density Assay
4.6. Luciferase Reporter Activity Assay
4.7. Protein Extraction and Immunoblot Analysis
4.8. Immunoprecipitation
4.9. Immunofluorescence and Confocal Fluorescence Microscopy
4.10. RNA Isolation and qPCR Analysis
4.11. Drosophila Studies
4.12. Mouse Studies
4.13. Human Studies
4.14. Study Approval
4.15. Statistics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Appendix A
Appendix B
Appendix C
Appendix D
References
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DUSP10 Cytoplasmic (n= 67) | DUSP10 Nuclei (n= 67) | |||||||
---|---|---|---|---|---|---|---|---|
Characteristic | No. of Patients a | Weak | Strong | p-Value b | Weak | Strong | p-Value b | |
COX2 cytoplasmic, No. (%) | ||||||||
Weak | 22 (32.8) | 8 (61.5) | 14 (25.9) | 0.022 | - | - | - | |
Strong | 45 (67.2) | 5 (38.5) | 40 (74.1) | - | - | - | ||
YAP1nuclei, No. (%) | ||||||||
Weak | 18 (28.6) | - | - | - | 8 (61.5) | 10 (20.0) | 0.006 | |
Strong | 45 (71.4) | - | - | - | 5 (38.5) | 40 (80.0) | ||
p-p38 staining, No. (%) | ||||||||
Positive | 2 (3.1) | 0 (0.0) | 2 (3.7) | 1.0 | 0 (0.0) | 2 (3.9) | 1.0 | |
Negative | 62 (96.9) | 10 (100.0) | 52 (96.3) | 13 (100.0) | 49 (96.1) |
Cytoplasmic DUSP10 (n = 961 ) | Nuclear DUSP10 (n = 961) | |||||||
---|---|---|---|---|---|---|---|---|
Categories | No. of Patients a | Weak | Strong | p-Value b | Weak | Strong | p-Value b | |
Sex, No. (%) | ||||||||
Female | 479 (49.8) | 293 (51.7) | 186 (47.2) | 0.190 | 235 (47.7) | 244 (52.1) | 0.176 | |
Male | 482 (50.2) | 274 (48.3) | 208 (52.8) | 258 (52.3) | 224 (47.9) | |||
Age, No. (%) | ||||||||
≤65 | 329 (34.2) | 199 (35.1) | 130 (33.0) | 0.457 | 155 (31.4) | 174 (37.2) | 0.156 | |
66-74 | 292 (30.4) | 172 (30.3) | 120 (30.5) | 159 (32.3) | 133 (28.4) | |||
≥75 | 340 (35.4) | 196 (34.6) | 144 (36.5) | 179 (36.3) | 161 (34.4) | |||
Stage, No. (%) | ||||||||
I | 136 (14.2) | 88 (15.6) | 48 (12.2) | 0.391 | 80 (16.2) | 56 (12.0) | 0.043 | |
II | 392 (40.9) | 232 (41.1) | 160 (40.7) | 201 (40.8) | 191 (41.1) | |||
III | 271 (28.3) | 147 (26.0) | 124 (31.6) | 140 (28.4) | 131 (28.2) | |||
IV | 159 (16.6) | 98 (17.3) | 61 (16.6) | 72 (14.6) | 87 (18.7) | |||
Unknown | 3 (0.3) | |||||||
Grade, No. (%) | ||||||||
Well differentiated | 96 (10.0) | 50 (8.8) | 46 (11.7) | 0.027 | 53 (10.8) | 43 (9.2) | 0.185 | |
Moderately differentiated | 607 (63.2) | 348 (61.4) | 259 (65.7) | 293 (59.4) | 314 (67.1) | |||
Poorly differentiated | 182 (18.9) | 118 (20.8) | 64 (16.2) | 108 (21.9) | 74 (15.8) | |||
Unknown | 76 (7.9) | |||||||
Chemotherapy, No. (%) | ||||||||
No | 673 (70.0) | 412 (72.7) | 261 (66.2) | 0.038 | 352 (71.4) | 321 (68.6) | 0.360 | |
Yes | 288 (30.0) | 155 (27.3) | 133 (33.8) | 141 (28.6) | 147 (31.4) | |||
Radiotherapy, No. (%) | ||||||||
No | 948 (98.6) | 557 (98.2) | 391 (99.2) | 0.259 | 485 (98.4) | 463 (98.9) | 0.580 | |
Yes | 13 (1.4) | 10 (1.8) | 3 (0.8) | 8 (1.6) | 5 (1.1) |
Nuclear DUSP10 | No. of Patients | No. of Death | RR Univariate (95% CI) | p-Value a | RR Adjusted 1 (95% CI) | p-Value a | RR Adjusted 2 (95% CI) | p-Value a | |
---|---|---|---|---|---|---|---|---|---|
Weak | 481 | 211 | 1 [Reference] | 0.047 | 1 [Reference] | 0.033 | 1 [Reference] | 0.189 | |
Strong | 459 | 213 | 1.22 (1.00–1.49) | 1.24 (1.02–1.51) | 1.14 (0.94–1.39) |
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Share and Cite
Jiménez-Martínez, M.; Ostalé, C.M.; van der Burg, L.R.; Galán-Martínez, J.; Hardwick, J.C.H.; López-Pérez, R.; Hawinkels, L.J.A.C.; Stamatakis, K.; Fresno, M. DUSP10 Is a Regulator of YAP1 Activity Promoting Cell Proliferation and Colorectal Cancer Progression. Cancers 2019, 11, 1767. https://doi.org/10.3390/cancers11111767
Jiménez-Martínez M, Ostalé CM, van der Burg LR, Galán-Martínez J, Hardwick JCH, López-Pérez R, Hawinkels LJAC, Stamatakis K, Fresno M. DUSP10 Is a Regulator of YAP1 Activity Promoting Cell Proliferation and Colorectal Cancer Progression. Cancers. 2019; 11(11):1767. https://doi.org/10.3390/cancers11111767
Chicago/Turabian StyleJiménez-Martínez, Marta, Cristina M. Ostalé, Lennart R. van der Burg, Javier Galán-Martínez, James C. H. Hardwick, Ricardo López-Pérez, Lukas J. A. C. Hawinkels, Konstantinos Stamatakis, and Manuel Fresno. 2019. "DUSP10 Is a Regulator of YAP1 Activity Promoting Cell Proliferation and Colorectal Cancer Progression" Cancers 11, no. 11: 1767. https://doi.org/10.3390/cancers11111767