Dr. Sossey-Alaoui research interests are in the area of studies of breast cancer, with special emphasis on Triple Negative Breast Cancer (TNBC) subtype. For the past 20 years I have been investigating the signaling pathways that promote the invasion-metastasis cascade of TNBC tumors. My laboratory investigates the molecular mechanisms that regulate the epithelial- mesenchymal transition (EMT) program, as well as the those that mediate the cancer stem cell phenotype and chemoresistance in TNBC. Our major active research projects include:
1- Role of WAVE3 in TNBC progression and metastasis: We established WAVE3, an actin cytoskeleton remodeling and scaffolding protein, as a novel promoter of TNBC development and metastatic progression, doing so by stimulating their acquisition of EMT, invasive, and metastatic phenotypes. Our recent investigations identified a role for WAVE3 in stabilizing β-catenin and, therefore, activating the downstream oncogenic pathways.
2- Role of YB1 in the invasion-metastasis cascade of TNBC, chemoresistance and cancer health disparities: YB1 is a multifunctional protein that regulates mRNA stability in the cytoplasm, and, in the nucleus, acts as a cancer stem cell (CSC) transcription factor. Targeted-inhibition of YB1 sensitizes TNBC cells to chemotherapy-and radiation-induced cell death, and inhibits progression and metastasis of TNBC tumors by targeting the CSC phenotype. We also identified a potential role of YB1 in the regulation of cell cycle, involving CDK2 and CDK4. More recently, we identified YB1 as being disparately activated in African American (AA) women with TNBC, compared to their Caucasian American (CA) counterparts. Increased YB1 activity correlates with increased resistance to chemotherapy and with worse disease outcomes in AA TNBC. We are currently investigating signaling pathways that involved the YB1-mediated regulation of immune- evasion in TNBC.
3- Kindlin-2 as a major regulator of the oncogenic signaling of TGF-β and cancer cell senescence: We also established Kindlin-2 as a major player in the modulation of the tumor microenvironment by regulating the CSF-1:EGF:TGF-β signaling axis and a key regulator of EMT during the invasion-metastasis cascade of TNBCs. Kindlin-2 acts as a physical bridge that links TGFbR1 and Integrins to activate the non-canonical TGF-β oncogenic signaling. In the nucleus,
Kindlin-2 associate with p53 to regulate cancer cell senescence through the activation of SepinB2/p21/AURK-A signaling axis.
4- Role of WAVE2 breast cancer progression and metastasis. The interplay between WAVE2 and miR-29 regulates the integrin-mediated modulation of the extracellular matrix and the downstream STAT3 oncogenic signaling in breast cancer.
MetroHealth Center for Cancer Research Website: https://www.metrohealth.org/center-for-cancer-research/researchers