High FMNL3 expression promotes nasopharyngeal carcinoma cell metastasis: role in TGF-β1-induced epithelia-to-mesenchymal transition

Abstract

Formin-like 3 (FMNL3) plays a crucial role in cytoskeletal mediation and is potentially a biomarker for cell migration; however, its role in cancer metastasis remains unknown. In this study, we found elevated FMNL3 protein expression in clinical nasopharyngeal carcinoma (NPC) tissues. FMNL3 expression positively correlated to the clinical stage, T (tumour), N (lymph node metastasis) and M (distant metastasis) classification of NPC patients. Moreover, FMNL3 positively correlated to Vimentin expression and negatively correlated to E-cadherin expression in clinical NPC samples. In vitro experiments showed that FMNL3 expression was inversely related to NPC cell differentiation status. Overexpression of FMNL3 led to epithelial-to-mesenchymal transition (EMT) in well differentiated CNE1 cells. TGF-β1-treated poorly differentiated CNE2 cells showed changes in EMT accompanied by enhanced FMNL3 expression and cell migration. On the contrary, knockdown of FMNL3 partially attenuated the TGF-β1-promoted CNE2 cell migration, together with associated changes in EMT markers. Finally, knockdown of FMNL3 also weakened EMT in tumours in xenographs. Our study indicates for the first time that TGF-β1/FMNL3 signalling may be a novel mechanism mediating EMT in NPC, which is closely associated with NPC metastasis.

High expression of FMNL3 associates with cancer cell migration, invasion, and unfavorable prognosis in tongue squamous cell carcinoma

“…FMNL3 is a newly discovered gene whose encoded product belongs to the DRFs family . Some studies showed that FMNL3 is highly expressed in a variety of malignant tumors and is associated with poor prognosis . Recent studies have also shown that members of the DRFs family induce pseudopodia by regulating the cytoskeletal network based on actin and tubulin, which promotes the migration and invasion of cancer cells .…”

“…Because FMNL3 overexpression is associated with poor prognosis of tongue cancer and it has been shown to promote the invasion and metastasis of cancer cells in a variety of malignancies, we further hypothesized that FMNL3 may influence tongue cancer metastasis. Metastasis is a complex process that requires tumor cells to transfer the cytoskeleton from the original tissue to a new focal point .…”

“…It is closely related to invasion and metastasis of tumors) . Studies have found that TGF‐β1/FMNL3 signaling may be a novel mechanism for mediating EMT in nasopharyngeal carcinoma and is closely related to NPC metastasis . Gardberg et al have shown that FMNL3 mediates the invasion and metastasis of melanoma through the RhoC pathway …”

“…8,9 Some studies showed that FMNL3 is highly expressed in a variety of malignant tumors and is associated with poor prognosis. [12][13][14] Recent studies have also shown that members of the DRFs family induce pseudopodia by regulating the cytoskeletal network based on actin and tubulin, which promotes the migration and invasion of cancer cells. 18 Based on these findings, we explored the expression of FMNL3 in TSCC tissue samples and performed thorough inquiries into the protein clinicopathological relevance and prognostic significance for patients with TSCC.…”

“…To further understand the impact of FMNL3 on the prognosis of tongue cancer, we analyzed the data of 90 cases of tongue cancer patients and divided them into high-expression and low-expression groups of FMNL3 according to IHC results. The expression of Because FMNL3 overexpression is associated with poor prognosis of tongue cancer and it has been shown to promote the invasion and metastasis of cancer cells in a variety of malignancies, [12][13][14] we further hypothesized that FMNL3 may influence tongue cancer metastasis.…”