How mammalian tissues maintain their architecture and tissue-specificity is poorly understood. Previously, we documented both the indispensable role of the extracellular matrix ECM protein, laminin LN1 , in the formation of normal breast acini, and the phenotypic reversion of cancer cells to acini-like structures in 3-dimensional 3D gels with inhibitors of oncogenic pathways. Here, we asked how laminin LN proteins integrate the signaling pathways necessary for morphogenesis.
These findings uncover the essential elements of breast epithelial architecture, where the balance between positive- and negative-players leads to homeostasis.
Most animal cells can secrete molecules into their surroundings to form a supportive meshwork of large proteins, called the extracellular matrix. This matrix is connected to the cell membrane through receptors that can transmit signals to the cell nucleus to change the levels of small RNA molecules called microRNAs.
These, in turn, can switch genes on and off in the nucleus. In the laboratory, cells that build breast tissue and glands can be grown in gels containing extracellular matrix proteins called laminins. However, if the communication between healthy cells and the extracellular matrix is interrupted, the cells can become disorganized and start to form clumps that resemble tumors, and if injected into mice, can form tumors.
Conversely, if the interaction between the extracellular matrix and the cells is restored, each single cancer cell can β despite mutations β be turned into a healthy-looking cell. These cells form a normal-looking tissue through a process called reversion. To investigate this, Furuta et al. The cells taken from the discarded tissue had been previously grown by a different group of researchers in a specific way to ensure that both normal and eventual cancer cells were from the same individual.
