The pathway allows stem cells to flip their orientation of cell division, switching their offspring between parallel basal cells and perpendicular luminal cells to form two distinct tissues found in the breast.
Some aggressive breast cancers use this mechanism to control the orientation of cancer cell division, so it could be a promising target for future drug development.
The study, published in the journal Cell Reports [1], was funded by Breakthrough Breast Cancer and conducted at The Institute of Cancer Research, London, with coordination from Cardiff University’s European Cancer Stem Cell Research Institute.
Team leader Dr Matt Smalley, a former Institute of Cancer Research scientist and currently Senior Lecturer at Cardiff University’s European Cancer Stem Cell Research Institute, said: “Current theories suggest that there may be similarities between the behaviour of normal adult stem cells and cancer cells. By better understanding the biology of adult stem cells scientists can better understand the behaviour of cancer cells and identify new targets for therapy.”
The mammary epithelium consists of two main types of cells: luminal epithelial cells, which line the ducts and form the milk-secreting cells of the alveoli, and basal myoepithelial cells, which squeeze milk along the ducts during lactation.
Basal stem cells are important during early breast development because they generate the different cell types in the mammary epithelium, through the expression of an enzyme called Aurora A. In this study, the researchers investigated how the enzyme Aurora A controls the formation of new cells in the breast.
Dr Smalley’s team identified for the first time a link between Aurora A and a signalling pathway known to regulate the behaviour of stem cells, called the NOTCH pathway. They found that Aurora A was able to control the direction of cell division in the breast by triggering the NOTCH signalling pathway.
The researchers found that for basal stem cells to maintain populations of basal and luminal cells, cell divisions in the basal layer of the breast needed to be parallel, which occurred when NOTCH signalling was blocked.
But they discovered that basal cells can also contribute to the luminal layer. Aurora A activated NOTCH signalling in the dividing basal cells, which caused their orientation to switch from parallel to perpendicular.
The ICR researchers were able to chemically control the signalling produced by the NOTCH pathway in normal cells, changing the number parallel basal cells and perpendicular luminal cells that were produced.
Dr Smalley believes that some aggressive breast cancers have re-activated this mechanism to control the orientation of cancer cell division, and that its discovery could lead to new treatments for breast cancer:
“If we can block this mechanism in breast cancer tumours, this could cause cells to try to divide in multiple directions at the same time, resulting in catastrophic disruption of genetic material and cell death,” said Dr Smalley.
“Our study suggests that drugs which can target this signalling mechanism could cause these cells to literally tear themselves apart, leading to better treatments for aggressive breast cancer in the future.”
- The paper published in the journal Cell Reports can be accessed by clicking here.