Scientists have identified a “master regulator” gene that, when repressed in cancer cells, puts a halt to tumours and stops them from enlarging and spreading to distant sites.
Researchers hope the gene may be the key to developing a new treatment for tumours resistant to current drugs.
This master regulator is normally turned off in adult cells, but it is very active during embryonic development and in all highly aggressive tumours studied to date,” said Linda Resar, from the Johns Hopkins University School of Medicine.
“Our work shows for the first time that switching this gene off in aggressive cancer cells dramatically changes their appearance and behaviour,” said Resar.
Resar has been investigating genes in the master regulator’s family, known as high mobility group or HMG genes, for two decades.
In addition to their role in cancer, these genes are essential for giving stem cells their special powers, and that’s no coincidence, she said.
“Many investigators consider cancer cells to be the evil twin of stem cells, because like stem cells, cancer cells must acquire special properties to enable the tumour to grow and metastasise or spread to different sites,” she said.
In the newly reported study, the Resar’s team applied the same techniques to several strains of human breast cancer cells in the laboratory, including the so-called triple negative cells – those that lack hormone receptors or HER2 gene amplification.
The Resar team blocked HMGA1 expression in aggressive breast cancer cells and followed their appearance and growth patterns.
“The aggressive breast cancer cells grow rapidly and normally appear spindle-shaped or thin and elongated. Remarkably, within a few days of blocking HMGA1 expression, they appeared rounder and much more like normal breast cells growing in culture,” said Resar.
The team also found that the cells with suppressed HMGA1 grow very slowly and fail to migrate or invade new territory like their HMGA1-expressing cousins.
Researchers next implanted tumour cells into mice to see how the cells would behave.
The tumours with HMGA1 grew and spread to other areas, such as the lungs, while those with blocked HMGA1 did not grow well in the breast tissue or spread to distant sites.