NCAM regulates the proliferation, apoptosis, autophagy, EMT, and migration of human melanoma cells via the Src/Akt/mTOR/cofilin signaling pathway

Abstract

The neural cell adhesion molecule (NCAM) plays critical roles in multiple cellular processes in neural cells, mesenchymal stem cells, and various cancer cells. However, the effect and mechanism of NCAM in human melanoma cells are still unclear. In this study, we found that NCAM regulated the proliferation, apoptosis, autophagy, migration, and epithelial‐to‐mesenchymal transition of human melanoma cells by determining the biological behavior of NCAM knockdown A375 and M102 human melanoma cells. Further studies revealed that NCAM knockdown impaired the organization of actin cytoskeleton and reduced the phosphorylation of cofilin, an actin‐cleaving protein. When cells were transfected with cofilin S3A (dephosphorylated cofilin), biological behavior similar to that of NCAM knockdown cells was observed. Research on the underlying molecular mechanism showed that NCAM knockdown suppressed activation of the Src/Akt/mTOR pathway. Specific inhibitors of Src and PI3K/Akt were employed to further verify the relationship between Src/Akt/mTOR signaling and cofilin, and the results showed that the phosphorylation level of cofilin decreased following inhibition of the Src/Akt/mTOR pathway. These results indicated that NCAM may regulate the proliferation, apoptosis, autophagy, migration, and epithelial‐to‐mesenchymal transition of human melanoma cells via the Src/Akt/mTOR/cofilin pathway‐mediated dynamics of actin cytoskeleton.

Nujiangexanthone A Inhibits Hepatocellular Carcinoma Metastasis via Down Regulation of Cofilin 1

“…Therefore, the decrease in CFL1 expression after treatment of NJXA mainly destroyed the balance between F-actin and G-actin, which then further inhibited the cancer metastasis. Actin cytoskeleton not only plays an important role in cell migration, which has also been reported to regulate EMT in metastatic cancer (Shankar and Nabi, 2015;Li et al, 2020). Our study here also found that after treatment with NJXA, the expression of EMT markers was down regulated, such as snail and vimentin, while E-cadherin was up regulated (Supplementary Figure 6).…”

“…It is well known that the inhibition of LIM kinase 1 downregulated CFL1 phosphorylation, which then suppresses the motility of cancer cells (Lu et al, 2018). Recently, research found that the inactivation of the Src/Akt/mTOR pathway could also suppress the phosphorylation of CFL1, which then regulate the migration and EMT (Li et al, 2020;Kulkarni et al, 2021). It has been reported that induction of EMT promotes invasion and migration of cancer cells, and predicts poor prognosis in HCC patients (Wang G. et al, 2021).…”

Activation of Cofilin Increases Intestinal Permeability via Depolymerization of F-Actin During Hypoxia in vitro

“…The molecular mechanism might be associated with the redistribution of the TJ proteins ZO-1, occludin, and claudin-1 in cells caused by the caveolae-mediated endocytosis of TJ components. Other studies have revealed that several signaling pathways were involved in the cofilin-dependent actin homeostasis, such as EGFR/Src/Akt and RhoA/ROCK pathway (Li et al, 2019; Xue et al, 2019). In addition, work in cultured cells has uncovered the mechanism and regulation of actin-mediated TJ, including Arp2/3 complex (Kang et al, 2013).…”

Long non‐coding RNA HULC stimulates the epithelial–mesenchymal transition process and vasculogenic mimicry in human glioblastoma

“…It is possible that lncRNA HULC may enhance the HIP-1αrelated PI3K/AKT/mTOR signaling, which cross-talks with the Wnt/β-catenin signaling to upregulate TGF-β and Snail expression, promoting the EMT process in GBM cells. [21][22][23] We are interested in further investigating the molecular mechanisms by which lncRNA HULC regulates the process of EMT and VM in GBM.…”