| Note | |
| | |
| Entity | Solid tumors |
| Disease | Papillary thyroid cancer, pancreatic cancer, prostate cancer, melanoma tumors |
| Oncogenesis | Rap1GAP, which acts as a GTPase activator for the nuclear Ras-related regulatory protein Rap1, was a specific negative regulator of Rap1, and the monomeric G protein Rap1 has been implicated in cancer tumorigenesis. It signals to pathways involved in cell adhesion, migration, and survival. Loss of Rap1GAP was discovered in papillary thyroid cancer, pancreatic cancer, prostate cancer, melanoma tumors, and their cell lines, all of them exhibited increased Rap1 activity, that activation of Rap1 promotes cell proliferation and migration potentiality through the mitogen-activated protein kinase pathway and integrin activation. As a putative tumor suppressor gene, Rap1GAP inhibits tumor growth but induces MMP2- and MMP9-mediated squamous cell carcinoma invasion and tumor progression, suggesting a role for this protein as a biomarker for early N-stage, aggressive squamous cell carcinomas. |
| | |
| | |
| Entity | Myelodysplastic syndrome (MDS) |
| Disease | The expression level of Rap1GAP in MDS patients significantly increased as compared with patients with non-malignant blood diseases or acute myeloid leukemia (AML). Among MDS patients, the expression level of Rap1GAP in MDS-refractory anemia (RA) was significantly higher than that in MDS-refractory anemia with excess of blasts (RAEB).
On the other hand, inhibiting Rap1 activity by expression of Rap1GAP increased leukocyte transendothelial migration, providing physiological relevance to the hypothesis that Rap1 augments barrier function of inter-endothelial cell junctions, implying the relevance of Rap1GAP in the regulation of haematogenesis. |
| | |
| Activation of Rap1 promotes prostate cancer metastasis. |
| Bailey CL, Kelly P, Casey PJ. |
| Cancer Res. 2009 Jun 15;69(12):4962-8. Epub 2009 May 26. |
| PMID 19470770 |
| |
| Protein RAP1GAP in human myelodysplastic syndrome detected by flow cytometry and its clinical relevance. |
| Ika SA, Qi XF, Chen ZX. |
| Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2009 Jun;17(3):612-7. |
| PMID 19549374 |
| |
| Rap1GAP promotes invasion via induction of matrix metalloproteinase 9 secretion, which is associated with poor survival in low N-stage squamous cell carcinoma. |
| Mitra RS, Goto M, Lee JS, Maldonado D, Taylor JM, Pan Q, Carey TE, Bradford CR, Prince ME, Cordell KG, Kirkwood KL, D'Silva NJ. |
| Cancer Res. 2008 May 15;68(10):3959-69. |
| PMID 18483282 |
| |
| Loss of Rap1GAP in papillary thyroid cancer. |
| Nellore A, Paziana K, Ma C, Tsygankova OM, Wang Y, Puttaswamy K, Iqbal AU, Franks SR, Lv Y, Troxel AB, Feldman MD, Meinkoth JL, Brose MS. |
| J Clin Endocrinol Metab. 2009 Mar;94(3):1026-32. Epub 2008 Dec 9. |
| PMID 19066305 |
| |
| Expression of Rap1GAP in human myeloid disease following microarray selection. |
| Qi X, Chen Z, Qian J, Cen J, Gu M. |
| Genet Mol Res. 2008 Apr 29;7(2):379-87. |
| PMID 18551404 |
| |
| Rap1 GTPase inhibits leukocyte transmigration by promoting endothelial barrier function. |
| Wittchen ES, Worthylake RA, Kelly P, Casey PJ, Quilliam LA, Burridge K. |
| J Biol Chem. 2005 Mar 25;280(12):11675-82. Epub 2005 Jan 20. |
| PMID 15661741 |
| |
| Identification of a putative tumor suppressor gene Rap1GAP in pancreatic cancer. |
| Zhang L, Chenwei L, Mahmood R, van Golen K, Greenson J, Li G, D'Silva NJ, Li X, Burant CF, Logsdon CD, Simeone DM. |
| Cancer Res. 2006 Jan 15;66(2):898-906. |
| PMID 16424023 |
| |
| Rap1GAP inhibits tumor growth in oropharyngeal squamous cell carcinoma. |
| Zhang Z, Mitra RS, Henson BS, Datta NS, McCauley LK, Kumar P, Lee JS, Carey TE, D'Silva NJ. |
| Am J Pathol. 2006 Feb;168(2):585-96. |
| PMID 16436672 |
| |
| Down-regulation of Rap1GAP via promoter hypermethylation promotes melanoma cell proliferation, survival, and migration. |
| Zheng H, Gao L, Feng Y, Yuan L, Zhao H, Cornelius LA. |
| Cancer Res. 2009 Jan 15;69(2):449-57. |
| PMID 19147557 |
| |
