Flotillin-2 promotes metastasis of nasopharyngeal carcinoma by activating NF-κB and PI3K/Akt3 signaling pathways

Abstract

Lipid raft proteins have been confirmed to be important in cell signal transduction. Some reports have shown that the aberrant expression of lipid raft proteins is associated with malignant phenotypes in some cancers. However, the role of the lipid raft protein flotillin-2 (Flot-2) in nasopharyngeal carcinoma (NPC) remains to be comprehensively characterized. Here, overexpression of Flot-2 in NPC tissues and cell lines was detected by immunostaining, and Flot-2 expression was found to be positively associated with NPC metastasis. Furthermore, inhibiting Flot-2 expression impaired the malignancy of the highly metastatic NPC cell line 5-8F by constraining its growth and proliferation, mobility and migration, and decreasing the capacity of 5-8F cells to metastasize in nude mice. In contrast, forced overexpression of Flot-2 increased the malignancy of 6-10B, a non-metastatic NPC cell line that weakly expresses Flot-2. Moreover, in 5-8F-shFlot-2 cells, which have inhibited Flot-2 expression, the NF-κB and PI3K/Akt3 pathways were inactivated. Subsequently, MMPs expression were decreased, and Foxo1 activity was increased. In addition, enhanced NF-κB and PI3K/Akt3 activities were observed in Flot-2 overexpressing 6-10B cells. Thus, Flot-2 exerts a pro-neoplastic role in NPC and is involved in tumor progression and metastasis. Moreover, Flot-2 exerts its role through NF-κB and PI3K/Akt3 signaling.

Flotillins: At the Intersection of Protein S-Palmitoylation and Lipid-Mediated Signaling

“…A co-localization of PI(4,5)P 2 and flotillins was also observed in pathological neuronal structures typical for the brains of Alzheimer's disease patients, suggesting their common involvement in neurodegeneration [136]. Flotillins have also been indicated as regulators of the PI3-kinase/AKT pathway crucial for cancer cell survival [137,138]. PI(4,5)P 2 can be enriched in rafts, and a significant elevation of its level in rafts occurs during the LPS-induced clustering of CD14, a GPI-anchored plasma membrane raft protein assisting the TLR4 receptor of macrophages in pro-inflammatory signal transduction [99,139].…”

MiR-20b targets AKT3 and modulates vascular endothelial growth factor-mediated changes in diabetic retinopathy

“…AKT3 belongs to the AKT family and has three closely-related isoforms AKT1, AKT2, and AKT3 that presumably play similar roles in cell proliferation, survival, metabolism, and many other cellular functions [28]. Various studies have shown that AKT3 plays an important role in cell migration in cancer [29][30][31], but little is known about the role of AKT3 in retinopathy. The role of AKT3 in angiogenesis has been implicated in several studies.…”

MicroRNA-485-5p suppresses the proliferation, migration and invasion of small cell lung cancer cells by targeting flotillin-2

“…SCLC has the pathological characteristics of high degree of malignancy, low degree of differentiation, rapid growth, invasion of blood vessels, early and extensive metastasis with poor biological behavior and dangerous prognosis. Moreover, SCLC patients are less symptomatic before diagnosis and survive shorter than patients with other types of lung cancer [4][5][6]. Although a number of studies have demonstrated that many molecular triggers play a vital role in the development of SCLC, the mechanisms underlying the process remain unclear.…”