Related Experiment Video
Updated: Jul 31, 2025
Portal Vein Injection of Colorectal Cancer Organoids to Study the Liver Metastasis Stroma
Published on: September 3, 2021
SH3BGRL Suppresses Liver Tumor Progression through Enhanced ATG5-Dependent Autophagy
Abdulmomen Ali Mohammed Saleh1,2, Farhan Haider2, Haimei Lv1
1Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Abstract:
SH3BGRL, an adaptor protein, is upregulated in breast cancers and indicates its tumorigenic role. But the function of SH3BGRL in other types of cancers is largely unknown. Here, we modulate SH3BGRL expression level in two liver cancer cells and conduct both in vitro and in vivo analyses of SH3BGRL in cell proliferation and tumorigenesis. Results demonstrate that SH3BGRL notably inhibits cell proliferation and arrests the cell cycle in both LO2 and HepG2 cells. Molecularly, SH3BGRL upregulates the expression of ATG5 from proteasome degradation as well as the inhibitions of Src activation and its downstream ERK and AKT signaling pathways, which eventually enhance autophagic cell death. The xenograft mouse model reveals that SH3BGRL overexpression can efficiently suppress tumorigenesis in vivo, while the additional silencing ATG5 in SH3BGRL-overexpressing cells attenuates the inhibitory effect of SH3BGRL on both hepatic tumor cell proliferation and tumorigenicity in vivo. The relevance of SH3BGRL downregulation in liver cancers and their progression is validated based on the large-scale tumor data. Taken together, our results clarify the suppressive role of SH3BGRL in tumorigenesis of liver cancer, which would be of help to the diagnosis of liver cancer, while either promoting the autophagy of liver cancer cells or inhibiting the downstream signaling induced from SH3BGRL downregulation would be a promising therapy.
Insights
SH3BGRL suppresses liver cancer growth by enhancing autophagy and inhibiting key signaling pathways. Its downregulation is linked to cancer progression, suggesting therapeutic potential.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- SH3BGRL, an adaptor protein, is known to be upregulated in breast cancers, suggesting a tumorigenic role.
- The function of SH3BGRL in other cancer types, particularly liver cancer, remains largely unexplored.
Purpose of the Study:
- To investigate the role of SH3BGRL in liver cancer cell proliferation and tumorigenesis.
- To elucidate the molecular mechanisms underlying SH3BGRL's function in liver cancer.
Main Methods:
- Modulation of SH3BGRL expression in liver cancer cell lines (LO2 and HepG2).
- In vitro assays assessing cell proliferation and cell cycle.
- In vivo studies using a xenograft mouse model.
- Analysis of molecular pathways including ATG5, Src, ERK, and AKT signaling.
Main Results:
- SH3BGRL overexpression significantly inhibits liver cancer cell proliferation and induces cell cycle arrest.
- SH3BGRL upregulates ATG5, inhibits Src activation, and suppresses downstream ERK/AKT signaling, promoting autophagic cell death.
- SH3BGRL overexpression suppresses in vivo tumor growth; ATG5 silencing attenuates this effect.
- SH3BGRL downregulation correlates with liver cancer progression in large-scale tumor data.
Conclusions:
- SH3BGRL plays a suppressive role in liver cancer tumorigenesis.
- SH3BGRL promotes autophagic cell death through ATG5 upregulation and inhibition of Src/ERK/AKT pathways.
- Targeting autophagy or SH3BGRL-related signaling pathways offers potential therapeutic strategies for liver cancer.
Related Concept Videos
02:23Abnormal Proliferation
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
01:22PI3K/mTOR/AKT Signaling Pathway