MARCKSL1 interacted with F‐actin to promote esophageal squamous cell carcinoma mobility by modulating the formation of invadopodia

Abstract

Background Emerging evidence indicates that myristoylated alanine‐rich C kinase substrate like 1 (MARCKSL1) is involved in the progression of esophageal squamous cell carcinoma (ESCC). However, the underpinning mechanism is unclear. Here, we investigated the mechanisms involving MARCKSL1 in ESCC progression. Methods CCK8, Transwell and wound‐healing assays were employed to test the effect of MARCKSL1 on proliferation, invasion and migration in vitro. Next, transcriptome profiling was conducted through RNA sequencing to reveal the underlying mechanism of MARCKSL1 in ESCC progression, which was subsequently verified by western blot and qPCR analysis. Moreover, immunofluorescence and gelatin degradation assays were performed to reveal the ability of MARCKSL1 to mediate invadopodia formation and extracellular matrix (ECM) degradation. Finally, the correlation between MARCKSL1 and the clinicopathological features of ESCC patients was assessed based on TCGA database analysis and immunohistochemistry staining of tissue microarrays. Results Knockdown of MARCKSL1 markedly attenuated the cell motility capacity of ESCC cells in vitro, while MARCKSL1 overexpression had the opposite effect. Transcriptomic analysis showed that MARCKSL1 mediated the mobility and migration of ESCC cells. In addition, overexpression of MARCKSL1 increased the colocalization of F‐actin and cortactin at the frontier edge of migrating cells and ECM degradation. Furthermore, in ESCC patients, the mRNA level of MARCKSL1 in esophageal carcinomas ( n = 182) was found to be notably higher than that in adjacent esophageal epithelia ( n = 286) and the expression levels of MARCKSL1 in the tumor tissues ( n = 811) were significantly increased compared to those in noncancerous esophageal tissues ( n = 442) with a large sample size. Higher expression of MARCKSL1 was positively correlated with lymph node metastasis and associated with worse survival rates of patients with ESCC. Conclusion MARCKSL1 promotes cell migration and invasion by interacting with F‐actin and cortactin to regulate invadopodia formation and ECM degeneration. High MARCKSL1 expression is positively correlated with poor prognosis in ESCC patients with lymph node metastasis.

Investigating cellular similarities and differences between upper tract urothelial carcinoma and bladder urothelial carcinoma using single-cell sequencing

“…MARCKS, known as myristoylated alanine-rich C kinase substrate, is an autophagy-related gene. Previous investigations have identified it as a diagnostic marker for gastric cancer ( 93 ), and has also been shown to enhance cell migration and invasion by interacting with F-actin and ECM degradation ( 94 ). Similarly, Chen et al.…”

Circulating extracellular vesicle-derived MARCKSL1 is a potential diagnostic non-invasive biomarker in metastatic colorectal cancer patients

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PHACTR1 promotes the mobility of papillary thyroid carcinoma cells by inducing F-actin formation

“…F-actin is a functional structure for cell mobility. Myristoylated alanine-rich C kinase substrate like 1 (MARCKSL1) relies on its interaction with F-actin to strengthen the mobility of esophageal carcinoma cells [ 16 ]. Moreover, previous study demonstrated that local membrane protrusions by directed polymerization in anterior F-actin triggers cell migration [ 17 ].…”