β2-Chimaerin Deficiency Favors Polyp Growth in the Colon of Apc<sup>Min/+</sup> Mice
A Rho-GTPases are pivotal regulators of key cellular processes implicated in colorectal cancer (CRC) progression, yet the roles of their regulatory proteins, particularly GTPase-activating proteins (GAPs), remain poorly understood. This study focuses on β2-chimaerin, a Rac1-specific GAP, in Apc-driv...
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MDPI AG
2025-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/30/4/824 |
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| author | Eladio A. Velasco-Sampedro Cristina Sánchez-Vicente María J. Caloca |
| author_facet | Eladio A. Velasco-Sampedro Cristina Sánchez-Vicente María J. Caloca |
| author_sort | Eladio A. Velasco-Sampedro |
| collection | DOAJ |
| description | A Rho-GTPases are pivotal regulators of key cellular processes implicated in colorectal cancer (CRC) progression, yet the roles of their regulatory proteins, particularly GTPase-activating proteins (GAPs), remain poorly understood. This study focuses on β2-chimaerin, a Rac1-specific GAP, in Apc-driven tumorigenesis using the ApcMin/+ mouse model. We demonstrate that β2-chimaerin deficiency selectively promotes the growth of colonic polyps without influencing small intestinal polyp formation. Mechanistically, β2-chimaerin loss is associated with enhanced ERK phosphorylation, while canonical Wnt/β-catenin and E-cadherin pathways remain unaffected, suggesting its specific involvement in modulating proliferative signaling in the colon. Consistent with its tumor-suppressive role, bioinformatics analyses reveal that low β2-chimaerin expression correlates with poor prognosis in CRC patients. This study expands the understanding of Rho-GTPase regulatory mechanisms in intestinal tumorigenesis, providing a basis for future therapeutic strategies targeting Rho-GTPase pathways in CRC. |
| format | Article |
| id | doaj-art-657cbffe515b4d51b53b64582fa2d0c0 |
| institution | OA Journals |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-657cbffe515b4d51b53b64582fa2d0c02025-08-20T02:04:06ZengMDPI AGMolecules1420-30492025-02-0130482410.3390/molecules30040824β2-Chimaerin Deficiency Favors Polyp Growth in the Colon of Apc<sup>Min/+</sup> MiceEladio A. Velasco-Sampedro0Cristina Sánchez-Vicente1María J. Caloca2Instituto de Biomedicina y Genética Molecular (IBGM), CSIC-UVA, 47003 Valladolid, SpainInstituto de Biomedicina y Genética Molecular (IBGM), CSIC-UVA, 47003 Valladolid, SpainInstituto de Biomedicina y Genética Molecular (IBGM), CSIC-UVA, 47003 Valladolid, SpainA Rho-GTPases are pivotal regulators of key cellular processes implicated in colorectal cancer (CRC) progression, yet the roles of their regulatory proteins, particularly GTPase-activating proteins (GAPs), remain poorly understood. This study focuses on β2-chimaerin, a Rac1-specific GAP, in Apc-driven tumorigenesis using the ApcMin/+ mouse model. We demonstrate that β2-chimaerin deficiency selectively promotes the growth of colonic polyps without influencing small intestinal polyp formation. Mechanistically, β2-chimaerin loss is associated with enhanced ERK phosphorylation, while canonical Wnt/β-catenin and E-cadherin pathways remain unaffected, suggesting its specific involvement in modulating proliferative signaling in the colon. Consistent with its tumor-suppressive role, bioinformatics analyses reveal that low β2-chimaerin expression correlates with poor prognosis in CRC patients. This study expands the understanding of Rho-GTPase regulatory mechanisms in intestinal tumorigenesis, providing a basis for future therapeutic strategies targeting Rho-GTPase pathways in CRC.https://www.mdpi.com/1420-3049/30/4/824β2-chimaerinRac1GTPase-activating protein (GAP)Apccolon cancerERK |
| spellingShingle | Eladio A. Velasco-Sampedro Cristina Sánchez-Vicente María J. Caloca β2-Chimaerin Deficiency Favors Polyp Growth in the Colon of Apc<sup>Min/+</sup> Mice Molecules β2-chimaerin Rac1 GTPase-activating protein (GAP) Apc colon cancer ERK |
| title | β2-Chimaerin Deficiency Favors Polyp Growth in the Colon of Apc<sup>Min/+</sup> Mice |
| title_full | β2-Chimaerin Deficiency Favors Polyp Growth in the Colon of Apc<sup>Min/+</sup> Mice |
| title_fullStr | β2-Chimaerin Deficiency Favors Polyp Growth in the Colon of Apc<sup>Min/+</sup> Mice |
| title_full_unstemmed | β2-Chimaerin Deficiency Favors Polyp Growth in the Colon of Apc<sup>Min/+</sup> Mice |
| title_short | β2-Chimaerin Deficiency Favors Polyp Growth in the Colon of Apc<sup>Min/+</sup> Mice |
| title_sort | β2 chimaerin deficiency favors polyp growth in the colon of apc sup min sup mice |
| topic | β2-chimaerin Rac1 GTPase-activating protein (GAP) Apc colon cancer ERK |
| url | https://www.mdpi.com/1420-3049/30/4/824 |
| work_keys_str_mv | AT eladioavelascosampedro b2chimaerindeficiencyfavorspolypgrowthinthecolonofapcsupminsupmice AT cristinasanchezvicente b2chimaerindeficiencyfavorspolypgrowthinthecolonofapcsupminsupmice AT mariajcaloca b2chimaerindeficiencyfavorspolypgrowthinthecolonofapcsupminsupmice |