SEPT7 overexpression inhibits glioma cell migration by targeting the actin cytoskeleton pathway

Abstract

Glioma cell metastasis is a serious obstacle for surgical treatment and prognosis, of which locomotion of the cytoskeleton is a key contributor of cancer cell spreading. SEPT7 is documented as a cytoskeletal protein with GTPase activity and involved in glioma progression. However, the underlying mechanism of SEPT7 in glioma invasion remains unresolved. Our study investigated whether SEPT7 influences glioma cell migration involved in cytoskeleton modulation. The SEPT7 expression in various glioma cell lines was markedly decreased compared to in normal human brain cells. It was demonstrated that SEPT7 overexpression significantly inhibits LN18 cell migration and chemotaxis induced by IGF‑1 (P<0.01 and P<0.01). Moreover, MMP‑2 and MMP‑9 were dramatically depressed after SEPT7 upregulation. To understand the mechanisms by which SEPT7 modulates homeostasis of the actin cytoskeleton, the F‑actin/G‑actin ratio and cofilin expression were determined. The data revealed that the F‑actin/G‑actin ratio and cofilin were reduced, and p‑cofilin increased conversely in cells with SEPT7 overexpression, indicating that SEPT7 reduced glioma cell migration by promoting cofilin phosphorylation and depolymerizing actin. Then, to understand the role of cofilin in SEPT7‑mediated actin dynamic equilibrium and cell migration, cofilin siRNA was transfected into cells. Surprisingly, cell migration and actin polymerization which had been improved by SEPT7 siRNA were significantly reversed, and the accompanying cofilin phosphorylation increased, indicating that cofilin phospho‑regulation played an important role in SEPT7‑mediated cytoskeleton locomotion and glioma cell migration. In conclusion, SEPT7 is involved in glioma cell migration with the assistance of cofilin phospho‑mediated cytoskeleton locomotion.

High expression of GALNT7 promotes invasion and proliferation of glioma cells

“…There are a variety of intracellular actin binding proteins that regulate multiple cellular functions, including changes in the structure of the actin cytoskeleton, which occur through the binding or dissociating of the proteins with actin ( 30 ). Regulation of the actin cytoskeleton pathway governs the cell motility of glioma by regulating the locomotion of the cytoskeleton, and slows the recovery of patients with glioma ( 31 , 32 ).…”

NKCC1 Regulates Migration Ability of Glioblastoma Cells by Modulation of Actin Dynamics and Interacting with Cofilin

“…Cofilin 1 has been reported to be upregulated in multiple highly invasive cancers including breast, colon and glioma where it plays a crucial role in cell motility and invasion (Sidani et al, 2007, Park et al, 2014, van Rheenen et al, 2009). Several studies have investigated the role of Cofilin 1 activity and its regulation in GBM, revealing that Cofilin 1 is overexpressed in gliomas and can alter GBM migration (Starinsky-Elbaz et al, 2009, Hou et al, 2016, Yap et al, 2005, Park et al, 2014). The outcome of Cofilin inhibition on cell migration is variable because it can modulate migration in opposite directions.…”

“…Different levels of overexpression can reduce or increase cell migration and invasion (Yap et al, 2005). In addition, there are some reports in GBM that show opposite effects in cell migration outcome depending of the level of phosphorylated Cofilin (inactive form) (Park et al, 2014, Hou et al, 2016, Zhou et al, 2016, Jin et al, 2016). This finding might be due to the fact that altering different components of the Cofilin pathway in heterogeneous tumors can have diverse effects on invasive potential (van Rheenen et al, 2009).…”

The role of septin 7 in physiology and pathological disease: A systematic review of current status

“…In CVPTC group, the septin 7 expression was only decreased in the nucleus while its overall and cytoplasmic expressions were stable . The difference in septin 7 expression patterns between FVPTC and CVPTC may be associated with different molecular regulatory mechanisms and signalling pathways …”

“…106 The difference in septin 7 expression patterns between FVPTC and CVPTC may be associated with different molecular regulatory mechanisms and signalling pathways. 99,112 9.3 | Septin 7 inhibits proliferation of HCC Hepatocellular carcinoma is the primary tumour of the liver. It may result from chronic alcoholism and viral hepatitis infection.…”