The invasion and metastasis of cancer was long thought to occur after cancer cells become highly malignant, however recent research has shown that in breast cancer, invasion and metastasis occur even during the early stages of carcinogenesis. Such spreading of tumor cells from the early stages of oncogenesis is an important factor to take into account when considering the prognosis of patients after initial treatment. Around 80% of human breast cancers arise from the luminal epithelium. The mammary gland is a milk producing exocrine organ, demonstrating a typical structure of the luminal epithelium, consisting of in addition to a luminal epithelial layer, a myoepithelial cell layer and basal membrane layer.

In order for cancerous epithelial cells to invade and metastasize, they must acquire “motility” at least transiently by altering their adhesive properties with neighboring cells and matrices. At the same time, they must avoid “anoikis: cell death due to loss of anchor” which normally forbids the survival of unanchored cells. Such processes are highly similar to “Epithelial-Mesenchymal-Transition (EMT)”, which is observed during development as well as during the reorganization of mammary gland lumen structures and the healing of an injury, and in addition, occurrence of EMT in mammary gland cancer cells is accompanied by the local disruption of epithelial lumen tissue. We have been continuously researching towards elucidation of the signaling molecules and pathways that confer cells with motility and give rise to EMT. Cancer is a disease caused by mutations in the genome. In this research project, using breast cancer as our main subject, we aim to elucidate the major signaling molecules and pathways that are involved in EMT of the luminal epithelium, as well as to clarify what changes occur at the genomic level to give rise to such signaling pathways. Our research would contribute towards elucidating the molecular mechanisms involved in cancer invasion and metastasis, especially the spread of cancer cells in the early stages of oncogenesis, and will provide information contributing towards further cancer research, as well as towards the prevention and treatment of cancer.
(cited from H. Sabe, J. Biochem.149: 633-639)