Trainee Project
Role of claudin in the formation of brain metastasis from TNBC
2023/01/03 - 2023/06/16
Three major groups of tumors can be identified using the presence or the lack of three biomarkers: luminal tumors that express estrogen receptor alpha and progesterone receptor, HER2 "enriched" tumors that overexpress human EGF receptor 2, and triple negative breast cancer (TNBC) that do not express ERα, PR and HER2. Triple negatives breast cancer accounts for 15 to 20% of breast cancers and is more common in young women. TNBC can be particularly aggressive and has a higher risk of recurrence as compared to other subtypes of breast cancer. Indeed, these tumors become rapidly chemo-resistant and metastatic. A current location is brain metastasizes, which are specially dreaded as they drastically alter the life quality and expectancy, at short time.
In 40% of TNBC, the expression of claudin 1, a major constituent of tight junctions, has been shown to be absent or strongly diminished. Most studies reported that a loss of claudin 1 expression correlates with increased malignant and metastasis potential associated with recurrence of disease in invasive breast carcinoma patients and. We and others showed that the re-expression of claudin 1 was shown to be sufficient to inhibit cell migration, and decrease intercellular adhesion in triple-negative breast cancer cell line
The aim of the M2 is to answer the following biological questions: are Claudins ket protein in the formation of brain metastasis.
The M2 project will present 3 parts
1) Characterize the junction constituent in model of co-culture TNBC and endothelial cells
2) Study mechanisms of adhesion between TNBC "claudin 1 low" et endothelial cells
3) Are claudins important for the migrating capacity thought endothelial cells
TNBC, Brain metastasis, claudin 1, cell junction, cell migration
Biology, Signals and Systems in Cancer and Neuroscience