Related Experiment Video
Updated: Jul 2, 2025
08:12
Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
Published on: October 5, 2020
3.0K
SERPINE2 promotes liver cancer metastasis by inhibiting c-Cbl-mediated EGFR ubiquitination and degradation
Shiyu Zhang1,2,3,4, Xing Jia1,2,3,4, Haojiang Dai1,2,3,4
1Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P. R. China.
Cancer Communications (London, England)
|February 26, 2024
Summary
Serpin family E member 2 (SERPINE2) promotes liver cancer metastasis by stabilizing epidermal growth factor receptor (EGFR). Inhibiting the SERPINE2-EGFR pathway may offer a new liver cancer treatment strategy.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Liver cancer presents high morbidity and mortality rates.
- Serpin family E member 2 (SERPINE2) is implicated in the metastasis of various cancers.
- Understanding SERPINE2's role in liver cancer metastasis is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the mechanism by which SERPINE2 contributes to liver cancer metastasis.
- To identify SERPINE2 as a potential therapeutic target in liver cancer.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) database for DNA methylation and transcriptome data analysis.
- Performed RNA sequencing, cytokine assays, immunoprecipitation (IP), mass spectrometry (MS), protein stability, and ubiquitination assays.
- Employed patient-derived xenografts and tumor organoid models to assess SERPINE2's role in sorafenib treatment.
Main Results:
- SERPINE2, regulated by DNA methylation, was identified as a tumor promoter in liver cancer, with higher expression correlating with poor prognosis.
- SERPINE2 enhanced liver cancer metastasis by promoting cell pseudopodia formation, adhesion, cancer-associated fibroblast activation, extracellular matrix remodeling, and angiogenesis.
- SERPINE2 stabilized epidermal growth factor receptor (EGFR) by inhibiting its ubiquitination via competition with c-Cbl, thereby activating downstream signaling pathways.
- SERPINE2 knockdown enhanced the efficacy of sorafenib and lenvatinib in preclinical models by downregulating EGFR.
Conclusions:
- SERPINE2 promotes liver cancer metastasis by stabilizing EGFR through inhibition of c-Cbl-mediated ubiquitination.
- Targeting the SERPINE2-EGFR axis presents a promising therapeutic strategy for liver cancer.
Related Concept Videos
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.2K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.2K
03:03mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
02:38Mitogens and the Cell Cycle
6.5K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.5K
02:33Hedgehog Signaling Pathway
7.4K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.4K
01:22PI3K/mTOR/AKT Signaling Pathway
3.6K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.6K
01:19Interactions Between Signaling Pathways
6.3K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K