Basal-like breast cancers (BLBCs) express genes characteristic of myoepithelial/basal cells in the normal mammary gland and constitute up to 25 percent of all breast cancers. Chemotherapy is the only systemic therapy for BLBC, which preferentially affects younger women and African-American women and is associated with high histological grade, aggressive clinical behavior and a propensity to metastasize to the brain and lung. To date, little is known about the molecular basis of BLBC.
iPSC-derived mammary-like organoid.
The Cui Laboratory has found that the FOXC1 transcription factor, which is involved in embryonic development, is a critical biomarker for BLBC. FOXC1 overexpression induces breast cancer cell growth, migration, invasion and chemo resistance. The Cui Lab is now using cell models to identify the signaling pathways mediating the effect of FOXC1 on BLBC cell functions. We also exploit mammary-specific overexpression and knockout mouse models to determine whether FOXC1 regulates BLBC development in vivo and predisposes breast cancer to brain and lung metastasis. Furthermore, the Cui Lab intends to define the molecular mechanisms responsible for upstream regulation of FOXC1 overexpression in BLBC. By providing insight into the signaling mechanism for FOXC1 regulation of breast cancer cell function, this study will advance our understanding of BLBC development and facilitate establishing a critical functional marker for detection and diagnosis of BLBC. Results may warrant development and clinical investigation of agents that block FOXC1. Finally, understanding how FOXC1 expression is regulated may allow development of FOXC1-based strategies to prevent BLBC.
The Cui Laboratory was the first to generate functional human breast cells and 3-D breast ductal structure in a dish using human induced pluripotent stem cells (hiPSCs).
The Cui Lab is now exploring the bioengineering of a complete breast tissue that comprises breast epithelial cells, fat cells, fibroblasts, blood vessels and other cell types. This novel methodology can be used to study and pinpoint the effect of specific hormones or any environmental factors on human breast development and function at the molecular and cellular level, which has not been achieved to date. Previously, this type of work has been simulated only in mouse models. However, mouse mammary glands are different from humans’ in terms of structure, composition and developmental regulation. Our model system can also be used to recapitulate the development of breast cancer caused by exposure to toxic chemicals and environmental factors and to test potential cancer prevention strategies. For example, for the first time, the Cui Lab may be able to elucidate why BRCA1 mutations lead to breast cancer. If we succeed, the technology can be used to generate patient-specific breast tissue to replace plastic materials in human breast reconstruction after lumpectomy or mastectomy in breast cancer patients. Patient-specific breast tissue can also be used in plastic surgery for cosmetic purposes. The Cui Laboratory hopes that, ultimately, breast tissue bioengineering techniques, including 3-D printing, combined with leading-edge gene editing technology, can be used to repair or regenerate healthy human breast tissue.