Related Experiment Video
Updated: Mar 24, 2026
08:54
An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells
Published on: July 20, 2014
14.5K
Membrane Curvature Activates Src kinase and Promotes Metastatic Cancer Cell Survival
Wei Zhang1,2, He You1,2, Xinzhi Zou3,4
1Department of Chemistry, Stanford University, Stanford, CA, USA.
Biorxiv : the Preprint Server for Biology
|March 23, 2026
Summary
Detached cancer cells activate Src kinase through membrane curvature, a process termed curvature-induced kinase activation (CIKA). Inhibiting CIKA selectively kills detached cells and suppresses metastasis.
Area of Science:
- Biophysics
- Cell Biology
- Cancer Research
Background:
- Src family kinases (SFKs) are crucial in cancer metastasis.
- Regulation of SFKs by cell adhesion and receptors is known, but activation upon cell detachment is unclear.
Purpose of the Study:
- To elucidate the mechanism of Src activation in detached tumor cells.
- To identify novel therapeutic strategies targeting metastatic cancer.
Main Methods:
- Investigated curvature-induced kinase activation (CIKA) mechanism.
- Utilized TOCA mutants to disrupt CIKA.
- Assessed cell viability in detached vs. adherent states.
- Evaluated metastatic colonization in xenograft mouse models.
Main Results:
- Discovered that plasma membrane curvature directly activates Src.
- CIKA involves TOCA protein oligomerization, biomolecular condensation, and Src stabilization.
- CIKA inhibition impairs detached cell viability and suppresses metastatic colonization.
- Anchorage-independent survival is promoted by curvature-induced Src activation.
Conclusions:
- Membrane curvature acts as a direct biophysical activator of Src.
- CIKA is a critical pathway for detached cancer cell survival and metastasis.
- CIKA inhibition presents a potential therapeutic strategy against metastatic cancer.
Related Concept Videos
01:35Cancer Cell Migration through Invadopodia
3.5K
Invadosome is a broad category of cell surface structures with proteolytic activity that degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
3.5K
02:38Mitogens and the Cell Cycle
8.4K
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...
8.4K
01:07MAPK Signaling Cascades
9.1K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
9.1K
03:03mTOR Signaling and Cancer Progression
5.0K
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...
5.0K
03:03mTOR Signaling and Cancer Progression
1.6K
1.6K
02:30Metastasis
6.8K
Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
6.8K