title: Elevated expression of flotillin-1 is associated with lymph node metastasis and poor prognosis in early-stage cervical cancer.
abstract: Accumulating evidence has revealed that the expression of the lipid raft protein flotillin-1 is elevated in various human cancers, but the role flotillin-1 plays in the carcinogenesis of cervical cancer remains unclear. The expression profile of flotillin-1 was assayed using real-time PCR, western blotting, and immunohistochemical (IHC) staining in cervical cancer cell lines and cancer tissues with paired adjacent noncancerous cervical tissues. The expression of flotillin-1 protein was detected by IHC staining in a large cohort of 308 paraffin-embedded cervical cancer tissues. Ectopic expression and the short hairpin RNA interference approach were employed to determine the role of flotillin-1 in cervical cancer cell metastasis and the possible mechanism involved. Flotillin-1 expression protein and mRNA were significantly upregulated in cervical cancer cell lines and cancer tissues; elevated expression of flotillin-1 protein in early-stage cervical cancer was significantly associated with pelvic lymph node metastasis (P < 0.001), and was an independent predictive factor of poor overall survival. Moreover, flotillin-1 up- and downregulation remarkably affected cervical cancer cell motility and invasion, respectively, through epithelial-mesenchymal transition (EMT) regulated by the Wnt/β-catenin and nuclear factor-κB (NF-κB) pathways. Our results suggest that flotillin-1 facilitates cervical cancer cell metastasis through Wnt/β-catenin and NF-κB pathway-regulated EMT and that the flotillin-1 expression profile serves not only as novel predictor of pelvic lymph node metastasis, but also as neoteric risk factor for patients with early-stage cervical cancer.
authors.affiliation: Department of Gynecologic Oncology, The Third Affiliated Hospital of Kunming Medical University (Yunnan Tumor Hospital) 519 Kunzhou Road, Kunming 650118, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Internal Medicine, First People's Hospital of Nanning, Lang Dong Branch 9 Yuebing Road, 7th Floor, Nanning 530021, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Gynecologic Oncology, The Third Affiliated Hospital of Kunming Medical University (Yunnan Tumor Hospital) 519 Kunzhou Road, Kunming 650118, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Gynecologic Oncology, The Third Affiliated Hospital of Kunming Medical University (Yunnan Tumor Hospital) 519 Kunzhou Road, Kunming 650118, China.
authors.forename: Xiaoliu
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Gynecologic Oncology, The Third Affiliated Hospital of Kunming Medical University (Yunnan Tumor Hospital) 519 Kunzhou Road, Kunming 650118, China.
authors.forename: Xielan
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Gynecologic Oncology, The Third Affiliated Hospital of Kunming Medical University (Yunnan Tumor Hospital) 519 Kunzhou Road, Kunming 650118, China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Gynecologic Oncology, The Third Affiliated Hospital of Kunming Medical University (Yunnan Tumor Hospital) 519 Kunzhou Road, Kunming 650118, China.
authors.forename: Hongying
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Pathology, The Third Affiliated Hospital of Kunming Medical University (Yunnan Tumor Hospital) 519 Kunzhou Road, Kunming 650118, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Pathology, The Third Affiliated Hospital of Kunming Medical University (Yunnan Tumor Hospital) 519 Kunzhou Road, Kunming 650118, China.
authors.forename: Chengang
authors.initials: C
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Oncology in South China, Department of Experimental Research, Cancer Center, Sun Yat-sen University 651 Dongfeng Road East, Guangzhou 510060, China.
authors.forename: Libing
authors.initials: L
authors.lastname: Song
keywords: EMT; Flotillin-1; Wnt/β-catenin and NF-κB pathways; cervical cancer; lymph node metastasis; prognosis