EphB6 promotes anoikis by modulating EphA2 signaling
Mai Akada1, Kohei Harada2, Manabu Negishi3
1Laboratory of Molecular Neurobiology, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Cellular Signalling
|September 21, 2014
Summary
EphB6 suppresses cancer cell resistance to anoikis, a key step in metastasis. This protein interacts with EphA2, reducing its oncogenic signaling and preventing cancer cell survival upon detachment.
Area of Science:
- Oncology
- Cell Biology
- Molecular Signaling
Background:
- Anoikis resistance is crucial for cancer metastasis.
- EphA2 overexpression promotes anoikis resistance via Akt phosphorylation and Ephexin4 activation.
- EphB6 is often silenced in metastatic cancers, but its role is unclear.
Purpose of the Study:
- To investigate the role of EphB6 in regulating EphA2-mediated anoikis resistance.
- To elucidate the molecular mechanisms by which EphB6 influences EphA2 signaling.
Main Methods:
- Co-immunoprecipitation to assess EphA2-EphB6 interaction.
- Western blotting to detect EphA2 phosphorylation at serine 897.
- Analysis of anoikis resistance in MCF7 breast cancer cells with manipulated EphB6 expression.
- Assessment of Ephexin4 interaction with EphA2 and RhoG activation.
Main Results:
- EphB6 interacts with EphA2 and suppresses EphA2-mediated anoikis resistance in MCF7 cells.
- Knockdown of EphB6 enhances anoikis resistance.
- EphB6 expression reduces EphA2 phosphorylation at serine 897.
- EphB6 inhibits EphA2-Ephexin4 interaction and subsequent RhoG activation.
Conclusions:
- EphB6 acts as a negative regulator of EphA2 oncogenic signaling.
- EphB6 suppresses cancer cell metastasis by inhibiting anoikis resistance.
- Targeting the EphB6-EphA2 interaction could offer therapeutic strategies against metastatic cancers.
Related Concept Videos
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
1.8K
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.
1.8K
01:24Regulation of Angiogenesis and Blood Supply
2.9K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.9K
01:15Receptor Downregulation in MVBs
2.0K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.0K
02:38Mitogens and the Cell Cycle
6.3K
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...
6.3K
01:17The Extrinsic Apoptotic Pathway
6.1K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.1K
01:22PI3K/mTOR/AKT Signaling Pathway
5.1K
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...
5.1K