Fascin and esophageal squamous cell carcinoma

Abstract

In a cancer prevalence survey, China was recognized to have a high incidence of esophageal cancer.Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal cancer and accounts for the vast majority of cases every year. ESCC cases in China contribute toward nearly half of all new global cases each year. As one of the higher ESCC prevalence regions in China, the Chaoshan District of Guangdong Province is the only area on the Chinese coastline with such a distinguished profile. Our laboratory, which is located in the Chaoshan District, studies the biological function, molecular basis, regulation mechanisms, and clinical significance of abnormally expressed cellular cytoskeleton binding proteins in ESCC, such as ezrin, fascin, LCN2, LOXL2, and DSC2. In the present review, we summarized studies on fascin in ESCC reported by our laboratory and other laboratories around the world. In ESCC, fascin expression is highly upregulated at the mRNA and protein levels, and can serve as an early biomarker for tumor invasion and metastasis. Furthermore, fascin transcription is directly activated through Sp1 binding to its promoter; this process is enhanced through the phosphorylation of Sp1 by the epidermal grown factoractivated Mitogen-activated protein kinase (MAPK)/Extracellular signal-regulated kinase (ERK) (MEK)-ERK1/2 signaling pathway. Furthermore, the function of fascin is also regulated by posttranslational modifications. For instance, the phosphorylation of several amino acid residues of fascin inhibits ESCC cell behavior and filopodia formation. However, whether other types of fascin modifications exist remains unknown and requires further study.

Application of molecular dynamics simulation in biomedicine

“…(Fraternali, 2017; Wang et al, 2020). For example, it has been shown that mutation of fascin (an actin‐binding protein) can lead to structural changes and weaken its ability to bind actin filaments (F‐actin) (Cheng et al, 2017; Wu, Wen, et al, 2021; Zeng et al, 2017). On the contrary, protein mutations can lead to drug resistance, which increases the difficulty of treatment.…”

P300/CBP‐associated factor (PCAF)‐mediated acetylation of Fascin at lysine 471 inhibits its actin‐bundling activity and tumor metastasis in esophageal cancer

“…Fluorescence recovery after photobleaching (FRAP) analysis revealed that the dynamic life cycle of filopodia, which includes protrusion, retraction, and stationary stages, largely depends on the rapid association/disassociation cycles of Fascin from filopodial actin filaments [ 5 , 7 ]. To date, Fascin has been found to be abnormally upregulated in all studied forms of human carcinoma, including colon, pancreatic, breast, lung, gastric, ovarian, cervical, tongue, brain, and esophageal cancers [ 8 , 9 ], and associated with clinically aggressive phenotypes, poor prognosis, and short survival [ 10 ]. Thus, Fascin has emerged as a potential biomarker for cancer diagnosis and prognosis [ 10 , 11 , 12 ], as well as a promising molecular target for future cancer therapy [ 13 ].…”