CST1 Promoted Gastric Cancer Migration and Invasion Through Activating Wnt Pathway

Abstract

Introduction Gastric cancer is one of the main reasons of cancer-induced death, exploring the molecular mechanisms of gastric cancer progression is critical for gastric cancer therapy. Here, we studied the role of cysteine protease inhibitor CST1 in gastric cancer progression. Methods Matrigel-coated or -uncoated transwell assay was used to determine the effect of CST1 on gastric cancer invasion and migration, luciferase reporter system was used to determine the effect of CST1 on Wnt pathway activity. Results CST1 had high expression levels in gastric cancer tissues and cells, patients who had high CST1 expression had poor outcome. Overexpression of CST1 increased gastric cancer migration and invasion, while knockdown of CST1 suppressed gastric cancer migration invasion. Mechanism analysis showed CST1 promoted WNT signaling pathway activity, promoted the nuclear translocation of β-catenin and the expression of Wnt signaling targets. Inhibition of Wnt pathway in CST1 overexpression cells inhibited migration and invasion, suggesting CST1 promoted gastric cancer cell migration and invasion through activating the Wnt pathway. Conclusion In summary, we found CST1 promoted gastric cancer migration and invasion through activating Wnt signaling, providing a novel target for gastric cancer therapy.

Cystatin SN as a potential marker for gastric cancer and promotes gastric cancer progression

“…We analyzed the relationship between CST1 and gastric cancer prognosis and genetic alterations by Oncomine,Ualcan ,Kaplan-Meier Plotter and cBioPortal database, and clari ed the role of CST1 as a prognostic biomarker in gastric cancer, gastric cancer patients with high CST1 expression have poor prognosis. This is consistent with previous studies that con rmed the role of CST1 as a proto-oncogenic molecule in gastric cancer (9). In contrast, our study focused on con rming the role of CST1 in gastric cancer through TCGA cancer database and analyzed the expression and gene mutation of CST1 in gastric cancer.CST1 is an independent prognostic factor for non-small cell lung cancer (NSCLC) patients(16).CST1 is a prognostic marker and therapeutic target for colorectal cancer patients (17).…”

“…Elevated expression levels of CST1 in breast cancer are closely associated with the progression and prognosis of breast cancer(8). A study con rmed that CST1 promotes invasion of gastric cancer cells through activation of Wnt Pathway (9). Upregulation of CST1 promotes hepatocellular carcinoma progression and predicts a poor prognosis (10).…”

Retracted: Silencing of cystatin SN abrogates cancer progression and stem cell properties in papillary thyroid carcinoma

“…Previous data suggested that CST1 might regulate CSC properties in PTC via targeting ERβ [ 22 ], but the role of ERβ in regulating PTC malignancy was controversial, which played both tumor‐promoting [ 22 ] and ‐suppressing [ 36 , 37 ] roles in PTC. In addition, CST1 had also been reported to modulate the development of cancers via targeting multiple signaling pathways (PI3K, phosphatidylinositol 3‐kinase), such as ERα/PI3K/AKT/ERα loopback pathway [ 38 ], Wnt pathway [ 39 ] and so on, but future work was still needed to investigate the molecular mechanisms by which CST1 facilitated the development of PTC. In summary, up‐regulation of CST1 promoted cell growth, motility, EMT and CSC properties to facilitate PTC pathogenesis.…”

Development and Evaluation of Serum CST1 Detection for Early Diagnosis of Esophageal Squamous Cell Carcinoma

“…Chen et al found the aberrant expression of CST1 existed in both gastric cancer tissues and cells, and patients with high CST1 expression had poor outcomes. 21 Dai et al demonstrated that high CST1 expression was negatively correlated with survival of breast cancer patients and might serve as an independent prognostic factor for breast cancer, the same as ER status and nodal status. 19 Additionally, serum CST1 was also reported to be a valuable diagnostic biomarker for colorectal cancer by enzyme-linked immunosorbent assay (ELISA), manifested as a marked increase in sera of patients with colorectal cancer.…”