Objective: Estrogen receptor alpha 36 (ER-alpha 36), a truncated variant of ER-alpha, is different from other nuclear receptors of the ER-alpha family. Previous findings indicate that ER-alpha 36 might be involved in cell growth, proliferation, and differentiation in carcinomas and primarily mediates non-genomic estrogen signaling. However, studies on ER-alpha 36 and cervical cancer are rare. This study aimed to detect the expression of ER-alpha 36 in cervical cancer; the role of ER-alpha 36 in 17-beta-estradiol (E2)-induced invasion, migration and proliferation of cervical cancer; and their probable molecular mechanisms. Methods: Immunohistochemistry and immunofluorescence were used to determine the location of ER-alpha 36 in cervical cancer tissues and cervical cell lines. CaSki and HeLa cell lines were transfected with lentiviruses to establish stable cell lines with knockdown and overexpression of ER-alpha 36. Wound healing assay, transwell invasion assay, and EdU incorporation proliferation assay were performed to evaluate the migration, invasion, and proliferation ability. The phosphorylation levels of mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) signaling molecules were examined with western blot analysis. Results: ER-alpha 36 expression was detected in both cervical cell lines and cervical cancer tissues. Down regulation of ER-alpha 36 significantly inhibited cell invasion, migration, and proliferation. Moreover, upregulation of ER-alpha 36 increased the invasion, migration, and proliferation ability of CaSki and HeLa cell lines. ER-alpha 36 mediates estrogen-stimulated MAPK/ERK activation. Conclusion: ER-alpha 36 is localized on the plasma membrane and cytoplasm in both cervical cancer tissues and cell lines. ER-alpha 36 mediates estrogen-stimulated MAPK/ERK activation and regulates migration, invasion, proliferation in cervical cancer cells. (C) 2017 Elsevier Inc. All rights reserved.