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Published on: January 7, 2019
The oncogenic role of MST3 in human gastric cancer
Kuo-Ting Lee1, Chia-Lin Chang2, Chung-Yen Li2
1Department of Surgery, National Cheng Kung University Hospital Tainan, Taiwan, ROC.
Abstract:
MST3 (mammalian STE20-like kinase) is one of the protein kinase of the GCK III subfamily STE 20, and is known to play a role in cell growth and apoptosis. Our laboratory has demonstrated that MST3 promotes tumorigenicity through the VAV2/Rac1 signal axis in breast cancer. In this report, we further investigated the potential oncogenic role of MST3 in gastric cancer. Examination of tissue samples from 101 gastric cancer patients revealed that higher expression of MST3 was observed in tumor part with immunohistochemistry. Furthermore, high expression of MST3 predicts poor prognosis in gastric cancer patients. To investigate the function of MST3 in vitro, MKN45 and NCI-N87 cell lines were transfected with the MST3 shRNA and stable clones were established. Downregulation of MST3 inhibited cell proliferation. The p21 expression was enhanced by MST3 shRNA in MKN45 gastric cancer cell line. Finally, downregulation of MST3 attenuated the anchorage-independent growth in soft agar and tumor growth in NOD/SCID mice. Altogether, our results indicate that MST3 potentially plays an oncogenic role in gastric cancer.
Insights
Mammalian STE20-like kinase 3 (MST3) promotes gastric cancer growth and poor prognosis. Inhibiting MST3 suppressed tumor cell proliferation and growth, indicating its oncogenic role.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Mammalian STE20-like kinase 3 (MST3) is a protein kinase involved in cell growth and apoptosis.
- Previous research demonstrated MST3's role in promoting tumorigenicity in breast cancer via the VAV2/Rac1 signaling pathway.
Purpose of the Study:
- To investigate the potential oncogenic role of MST3 in gastric cancer.
- To determine the relationship between MST3 expression and patient prognosis.
Main Methods:
- Immunohistochemistry was used to examine MST3 expression in 101 gastric cancer patient tissue samples.
- Gastric cancer cell lines (MKN45 and NCI-N87) were transfected with MST3 shRNA to downregulate its expression.
- In vitro assays included proliferation, anchorage-independent growth in soft agar, and in vivo tumor growth in NOD/SCID mice.
Main Results:
- Higher MST3 expression was observed in gastric tumors compared to normal tissue.
- High MST3 expression correlated with poor prognosis in gastric cancer patients.
- Downregulation of MST3 inhibited gastric cancer cell proliferation, anchorage-independent growth, and tumor growth in mice.
- MST3 shRNA enhanced p21 expression in MKN45 cells.
Conclusions:
- MST3 plays a significant role in promoting gastric cancer progression.
- MST3 expression levels can serve as a prognostic marker for gastric cancer patients.
- Targeting MST3 may represent a potential therapeutic strategy for gastric cancer.
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