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Rab11a regulates MMP2 expression by activating the PI3K/AKT pathway in human hepatocellular carcinoma cells
Zhi-Yun Zhang1, Meng Lu1, Ze-Kun Liu1
1Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, 710032, China.
Abstract:
As a member of the Rab GTPase family, Rab11a plays an important role in vesicle transport and tumor progression. However, it is not clear whether it can also be used as an oncoprotein in hepatocellular carcinoma (HCC). In this study, database and immunohistochemical analyses showed that Rab11a was highly expressed in HCC tissues, and associated with poor clinical prognosis. Rab11a overexpression promoted the proliferation, migration, invasion, and anti-apoptosis of human HCC cell lines, MHCC-97H and HCC-LM3, whereas the downregulation of Rab11a inhibited these biological tumor activities. Nude mice xenograft demonstrated that Rab11a had a positive effect on the growth of hepatocellular carcinoma cells in vivo. Further studies found that the PI3K/AKT pathway and matrix metalloproteinase 2 (MMP2) upregulation can be activated by over-expression of Rab11a. However, MMP2 upregulation induced by Rab11a can be inhibited by the PI3K/AKT pathway inhibitor, LY294002. Altogether, our study established for the first time that Rab11a can play a pro-cancer role in HCC, as a novel oncoprotein, by activating the PI3K/AKT pathway to regulate MMP2 expression.
Insights
Rab11a acts as a novel oncoprotein in hepatocellular carcinoma (HCC). This study shows Rab11a promotes HCC growth and metastasis by activating the PI3K/AKT pathway, leading to matrix metalloproteinase 2 (MMP2) upregulation.
Area of Science:
- Molecular Biology
- Oncology
- Cell Biology
Background:
- Rab11a, a Rab GTPase, is implicated in vesicle transport and tumor progression.
- Its role as an oncoprotein in hepatocellular carcinoma (HCC) remains unclear.
Purpose of the Study:
- To investigate the role of Rab11a as an oncoprotein in HCC.
- To elucidate the underlying molecular mechanisms of Rab11a in HCC progression.
Main Methods:
- Database and immunohistochemical analyses of HCC tissues.
- In vitro studies using HCC cell lines (MHCC-97H, HCC-LM3) with Rab11a overexpression and downregulation.
- In vivo xenograft models in nude mice.
- Investigation of the PI3K/AKT pathway and MMP2 expression.
Main Results:
- Rab11a is highly expressed in HCC tissues and correlates with poor prognosis.
- Rab11a overexpression enhances HCC cell proliferation, migration, invasion, and anti-apoptosis.
- Rab11a downregulation inhibits these tumor activities.
- Rab11a promotes HCC growth in vivo.
- Rab11a activates the PI3K/AKT pathway, leading to MMP2 upregulation, which can be inhibited by LY294002.
Conclusions:
- Rab11a functions as a novel oncoprotein in HCC.
- Rab11a promotes HCC progression by activating the PI3K/AKT pathway to upregulate MMP2 expression.
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