Related Experiment Video
Updated: Jul 1, 2026
12:19
Three-Dimensional (3D) Tumor Spheroid Invasion Assay
Published on: May 1, 2015
Autocrine semaphorin3A stimulates alpha2 beta1 integrin expression/function in breast tumor cells.
Hongjie Pan1, Luke S Wanami, Thusitha R Dissanayake
1Department of Pathology, Duke University Medical Center, P.O. Box 3712 D.U.M.C., Durham, NC, 27710, USA.
Breast Cancer Research and Treatment
|September 13, 2008
Summary
Semaphorin3A (SEMA3A) signaling boosts alpha2beta1 integrin in breast cancer cells, enhancing collagen adhesion and suppressing migration. This autocrine pathway highlights SEMA3A
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Semaphorin3A (SEMA3A) and its receptor Neuropilin-1 (NP-1) are implicated in suppressing breast tumor cell migration.
- Both SEMA3A and alpha2beta1 integrin are known to inhibit breast tumor cell motility.
Purpose of the Study:
- To investigate the impact of SEMA3A signaling on alpha2beta1 integrin expression and function in breast tumor cells.
- To elucidate the molecular mechanisms by which SEMA3A influences breast tumor cell behavior.
Main Methods:
- Incubation of breast tumor cells with SEMA3A.
- Analysis of alpha2beta1 integrin levels and collagen I adhesion.
- Manipulation of SEMA3A expression.
- Assessment of actin cytoskeleton disruption, cell migration, and invasion.
- Use of alpha2beta1-neutralizing antibodies.
Main Results:
- SEMA3A increased alpha2beta1 integrin levels and adhesion to collagen I in breast tumor cells.
- Reduced SEMA3A expression led to decreased alpha2beta1 levels and collagen adhesion.
- SEMA3A-induced collagen adhesion was dependent on NP-1 and glycogen synthase kinase-3.
- SEMA3A disrupted the actin cytoskeleton, reducing tumor cell migration and invasion.
- SEMA3A's suppression of migration was dependent on alpha2beta1 integrin.
Conclusions:
- SEMA3A signaling stimulates alpha2beta1 integrin expression in breast tumor cells.
- An autocrine SEMA3A pathway promotes alpha2beta1 integrin expression, which suppresses metastatic breast tumor growth.
- Targeting the SEMA3A/alpha2beta1 axis may offer therapeutic strategies for breast cancer.
Related Concept Videos
01:17Intracellular Signaling Affects Focal Adhesions
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
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.
02:17The Tumor Microenvironment
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
01:15Activation of Integrins
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
01:01Autocrine Signaling
Autocrine signaling is one of the many signaling mechanisms that function inside multicellular organisms to carry out intercellular communication. In this type of signaling mechanism, the same cell that secretes an extracellular signaling molecule also expresses the receptors to bind and respond to that signaling molecule.
Autocrine Signaling in Macrophages
Under normal physiological conditions, autocrine signaling is essential for maintaining homeostasis. This process is well characterized in...
Autocrine Signaling in Macrophages
Under normal physiological conditions, autocrine signaling is essential for maintaining homeostasis. This process is well characterized in...
01:19Cadherins in Tissue Organization
The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Cell Sorting During Development
Cell sorting plays an...