DNA methylation dependent suppression of GPER1 in colorectal cancer

Main Article Content

Mohan C. Manjegowda Anil M. Limaye


A paper published by Liu and co-workers in a recent issue of Molecular Cancer not only reiterates the epigenetic silencing as a mechanism of GPER1 suppression, but also expands the scope of this emerging paradigm beyond breast cancer to include colorectal adenocarcinoma. This article is a commentary on the relevance and significance of their work. It presents results obtained through an independent analysis of TCGA-COADREAD dataset that supports their claim. It highlights the emerging role of DNA methylation in GPER1 regulation by drawing parallels with other published works, while at the same time draws attention of the readers to the caveats and the points of departures from recent literature.

Keywords: GPER1, GPR30, colorectal carcinoma, methylation, TCGA, CpG island shore

Article Details

How to Cite
MANJEGOWDA, Mohan C.; LIMAYE, Anil M.. DNA methylation dependent suppression of GPER1 in colorectal cancer. Medical Research Archives, [S.l.], v. 6, n. 4, aug. 2019. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/1728>. Date accessed: 25 mar. 2023. doi: https://doi.org/10.18103/mra.v6i5.1728.


1. Prossnitz ER, Barton M. Estrogen biology: New insights into GPER function and clinical opportunities. Mol Cell Endocrinol. 2014;1421. doi:10.1016/j.mce.2014.02.002.
2. Manjegowda MC, Gupta PS, Limaye AM. Hyper-methylation of the upstream CpG island shore is a likely mechanism of GPER1 silencing in breast cancer cells. Gene. 2017;614:65-73. doi:10.1016/j.gene.2017.03.006.
3. Weißenborn C, Ignatov T, Ochel H-J, et al. GPER functions as a tumor suppressor in triple-negative breast cancer cells. J Cancer Res Clin Oncol. 2014;140(5):713-23. doi:10.1007/s00432-014-1620-8.
4. Weißenborn C, Ignatov T, Poehlmann A, et al. GPER functions as a tumor suppressor in MCF-7 and SK-BR-3 breast cancer cells. J Cancer Res Clin Oncol. 2014;140(4):663-71. doi:10.1007/s00432-014-1598-2.
5. Weissenborn C, Ignatov T, Nass N, et al. GPER Promoter Methylation Controls GPER Expression in Breast Cancer Patients. Cancer Invest. 2017;35(2):1-8. doi:10.1080/07357907.2016.1271886.
6. Liu Q, Chen Z, Jiang G, et al. Epigenetic down regulation of G protein-coupled estrogen receptor (GPER) functions as a tumor suppressor in colorectal cancer. Mol Cancer. 2017;16(1):87. doi:10.1186/s12943-017-0654-3.
7. Muzny DM, Bainbridge MN, Chang K, et al. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012;487(7407):330-337. doi:10.1038/nature11252.
8. Wei W, Chen Z-J, Zhang K-S, et al. The activation of G protein-coupled receptor 30 (GPR30) inhibits proliferation of estrogen receptor-negative breast cancer cells in vitro and in vivo. Cell Death Dis. 2014;5(October 2016):e1428. doi:10.1038/cddis.2014.398.
9. Pandey DP, Lappano R, Albanito L, Madeo A, Maggiolini M, Picard D. Estrogenic GPR30 signalling induces proliferation and migration of breast cancer cells through CTGF. EMBO J. 2009;28(5):523-32. doi:10.1038/emboj.2008.304.
10. Pupo M, Pisano A, Abonante S, Maggiolini M, Musti AM. GPER activates Notch signaling in breast cancer cells and cancer-associated fibroblasts (CAFs). Int J Biochem Cell Biol. 2014;46:56-67. doi:10.1016/j.biocel.2013.11.011.
11. Lv X, He C, Huang C, et al. G-1 inhibits breast cancer cell growth via targeting colchicine-binding site of tubulin to interfere with microtubule assembly. Mol Cancer Ther. 2017:molcanther.0626.2016. doi:10.1158/1535-7163.MCT-16-0626.
12. Wang C, Lv X, Jiang C, Davis JS. The putative G-protein coupled estrogen receptor agonist G-1 suppresses proliferation of ovarian and breast cancer cells in a GPER-independent manner. Am J Transl Res. 2012;4(4):390-402. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3493027&tool=pmcentrez&rendertype=abstract.
13. Wang C, Lv X, He C, Hua G, Tsai M-Y, Davis JS. The G-protein-coupled estrogen receptor agonist G-1 suppresses proliferation of ovarian cancer cells by blocking tubulin polymerization. Cell Death Dis. 2013;4(10):e869. doi:10.1038/cddis.2013.397.