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Gastrokine 2 Regulates the Antitumor Effect of JAK2/STAT3 Pathway in Gastric Cancer
Yu Zhou1,2, Shan Xu3, Jiao Liu3,4
1The First Affiliated Hospital of Shaoyang University, Shaoyang, Hunan 422000, China.
Abstract:
GKN2 (gastrokine 2) mainly plays a regulatory role in gastric mucosal defense and cell protection mechanisms, and its role in gastric cancer has not been thoroughly elucidated. Immunohistochemistry was used to detect GKN2 and TFF1 expressions in 90 gastric cancer tissues, 48 neoplastic resection margins, and 22 normal gastric mucosa epithelia. It showed that the downregulation of GKN2 and TFF1 expressions in gastric cancer tissues was significantly different from that in adjacent normal gastric tissues and distal gastric mucosal tissues. Nevertheless, correlation analysis showed that GKN2 expression in gastric cancer tissues was independent of TFF1 expression. After overexpression of GKN2 was constructed in human gastric cancer cell line MKN28 with the Ad-GFP-GKN2 transfected, cell viability was measured by CCK-8 assay, and migration and invasion ability were analyzed by transwell migration assay and transwell invasion assay. It indicated that overexpression of GKN2 significantly reduced the viability of MKN28 and SGC7901 cells. Overexpression of GKN2 could also inhibit the migration and invasion ability in MKN28 and SGC7901 cells. In addition, upregulation of GKN2 can inactivate the JAK2/STAT3 pathway. Our data suggest that GKN2 and TFF1 play the antitumor role in gastric carcinoma, and TFF1 may not interact or cooperate with GKN2. GKN2 overexpression can inhibit the growth and metastasis by downregulating the JAK2/STAT3 pathway in gastric cancer cells.
Insights
Gastrokine 2 (GKN2) shows reduced expression in gastric cancer, inhibiting tumor growth and metastasis. Overexpression of GKN2 suppresses cancer cell viability and migration by inactivating the JAK2/STAT3 pathway.
Area of Science:
- Oncology
- Gastroenterology
- Molecular Biology
Background:
- Gastrokine 2 (GKN2) is implicated in gastric mucosal defense but its role in gastric cancer remains unclear.
- Gastric cancer is a significant health concern with complex underlying molecular mechanisms.
Purpose of the Study:
- To investigate the role of GKN2 in gastric cancer.
- To determine the effect of GKN2 overexpression on gastric cancer cell behavior and signaling pathways.
Main Methods:
- Immunohistochemistry to assess GKN2 and TFF1 expression in gastric tissues.
- Overexpression of GKN2 in gastric cancer cell lines (MKN28, SGC7901).
- Cell viability (CCK-8), migration, and invasion assays.
- Analysis of the JAK2/STAT3 pathway.
Main Results:
- GKN2 and TFF1 expression were downregulated in gastric cancer tissues compared to normal tissues.
- GKN2 expression was independent of TFF1 expression.
- Overexpression of GKN2 reduced gastric cancer cell viability, migration, and invasion.
- Upregulation of GKN2 inactivated the JAK2/STAT3 pathway.
Conclusions:
- GKN2 exhibits an antitumor role in gastric carcinoma.
- GKN2 overexpression inhibits gastric cancer growth and metastasis, potentially via JAK2/STAT3 pathway inactivation.
- TFF1 may not interact with GKN2 in gastric cancer.
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