The involvement of survivin in insulin-like growth factor 1-induced epithelial-mesenchymal transition in gastric cancer

Abstract

It has been identified that insulin-like growth factor 1 (IGF-1) activated various pathways of the epithelial-mesenchymal transition (EMT) in a couple of tumors. At the same time, survivin is implicated in EMT of gastric cancer (GC). To date, the impact of survivin on IGF-1-mediated EMT of GC has not been featured. In this work, we used the immunohistochemistry and molecular and cellular experiments to investigate the existence and significance of IGF-1 and survivin. Our findings revealed that survivin protein can be observed in majority of samples in all GC samples. Importantly, survivin expression has an obvious association with GC stage, and metastasis. In vitro, GC cell line BGC823 was treated with different concentrations of IGF-1, resulting in the activation of p-ERK, p-AKT, survivin, and the expression of EMT biomarkers, including N-cadherin, MMP2, and Snail. However, the silencing of survivin eradicated the expression IGF-1-induced EMT biomarkers and affected the migration and invasion of BGC823 cells. In conclusion, IGF-1 signaling activated survivin expression and controlled the expression of EMT biomarkers in the development of GC. This study lays a new stage for the molecular therapy of GC patients in the clinical treatment.

Molecular Signatures of the Insulin-Like Growth Factor 1-Mediated Epithelial-Mesenchymal Transition in Breast, Lung and Gastric Cancers

“…The invasive behavior and metastatic properties of GC are closely related to the EMT and high levels of some EMT markers in biopsy samples are hallmarks of poor prognosis [7,105,106,107,108,109,207,208]. IGF-1 signaling is the main EMT axis in GC and, in general, it follows RAS/MEK/ERK and PI3K/AKT routes, which are common to other types of cancer [105,207,208,209].…”

“…IGF-1 signaling is the main EMT axis in GC and, in general, it follows RAS/MEK/ERK and PI3K/AKT routes, which are common to other types of cancer [105,207,208,209]. The upregulation of ZEB2, but not of ZEB1, TWIST1 or TWIST2 is the main peculiarity of IGF-1-induced EMT in GC, at least in BGC-823 human gastric adenocarcinoma cells (Figure 1) [208].…”

“…Another possible crucial molecular regulator of IGF-1-mediated EMT in GC is survivin, whose expression has been associated with GC stage and metastasis (Figure 1) [207]. Indeed, IGF-1 treatment increases ERK and AKT phosphorylation in the GC cell line BGC823, and the expression of survivin and EMT biomarkers, including N-cadherin, MMP2, and SNAIL [207].…”

“…Indeed, IGF-1 treatment increases ERK and AKT phosphorylation in the GC cell line BGC823, and the expression of survivin and EMT biomarkers, including N-cadherin, MMP2, and SNAIL [207]. Silencing of survivin eradicates the expression of IGF-1-induced EMT biomarkers like N-cadherin, MMP2, and SNAIL, and negatively affects (reduces) the migration and invasion of BGC823 cells [207].…”

“…Indeed, IGF-1 treatment increases ERK and AKT phosphorylation in the GC cell line BGC823, and the expression of survivin and EMT biomarkers, including N-cadherin, MMP2, and SNAIL [207]. Silencing of survivin eradicates the expression of IGF-1-induced EMT biomarkers like N-cadherin, MMP2, and SNAIL, and negatively affects (reduces) the migration and invasion of BGC823 cells [207]. Moreover, interferon induces transmembrane protein 2 (IFITM2), thought to act as a tumor suppressor, promotes cancer cell proliferation, invasion, migration and the EMT in vitro, as well as tumor growth and metastasis in an xenograft model [136].…”