Abstract
Invasion and metastasis are critical pathological and mortal processes in esophageal squamous cell carcinoma (ESCC). Novel drugs, targeting the two cancer migration stages, will augment the treatment options for ESCC therapy and improve overall survival. A novel natural macrolide F806 specifically promotes apoptosis of various ESCC cells. However, whether F806 can inhibit metastasis of ESCC cells needs further evaluation. Here, our data showed that F806 inhibits dynamic F-actin assembly and then suppresses the migration of ESCC cells in vitro and their invasion and metastasis in vivo. The correlation between cancer migration and actin cytoskeleton assembly was consistent with the ability of F806 to prevent the aggregation of Paxillin, an essential protein for focal adhesion formation through binding to the ends of actin filaments. Furthermore, F806 downregulated the expression and activity of the Rho family proteins cell division cycle 42 (CDC42), RAC family small GTPase 1 (RAC1), and RAS homolog family member A (RHOA). Taken together, these results suggest that F806 can suppress cancer invasion and metastasis via interrupting the assembly of migration components involving F-actin.
Highlights
Esophageal cancer (EC) has the characteristics of rapid progression, poor prognosis, and poor survival, which make it the eighth most common and sixth most fatal cancer worldwide [1, 2]
The results indicated that the migration of esophageal squamous cell carcinoma (ESCC) cells in vitro was clearly suppressed by F806
Since Rho family proteins regulate the attachment of actin cytoskeleton to focal adhesion [24] and Paxillin is one of the key focal adhesion-associated proteins [25], we evaluated the actin assembly by detecting the location of Paxillin
Summary
Esophageal cancer (EC) has the characteristics of rapid progression, poor prognosis, and poor survival, which make it the eighth most common and sixth most fatal cancer worldwide [1, 2]. ESCC is usually diagnosed at advanced stages and the 5-year overall survival rate of the patients with metastatic disease is less than 10% [6, 7], which partly results from the insufficient drugs that target ESCC metastasis. ESCC metastasis requires cells to access invasive and migratory processes, which are initiated by the dynamic assembly of actin cytoskeleton into filopodia and microspike structures [9]. It can be said that the BioMed Research International dynamic regulation of actin cytoskeleton and the action of its regulatory proteins are still worthy of study, especially in the context of target drug treatment for metastatic ESCC patients
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
