Biomedical scientists have discovered a protein called SAS-6 that controls how cells divide can stave off the spread of cancer.
SAS-6 makes cells grow more and longer cilia – tiny antennae that sense their surroundings. These cilia activate a pathway known as YAP/TAZ, which controls genes that help tumours grow and spread to other parts of the body.
Researchers now believe SAS-6 might be a warning sign for aggressive cancers – and a new target for drugs to block metastasis before it begins.
For the first time, scientists have shown that a protein that helps a cell prepare to divide can also trigger the spread of cancer.
The protein, called SAS-6, plays a role in building tiny hair-like structures on the cell’s surface, which in turn activate signals that make cancer cells more aggressive.
“Our data uncover a novel role for the centriolar protein SAS-6 in ciliogenesis, YAP activation and cancer cell invasion,” said Brunel University of London’s Dr Barbara Tanos.
“The main cause of death in cancer patients is metastatic disease, which happens when cancer cells invade tissues far away from the main tumour,” Dr Tanos explains. “We found that cells with increased SAS-6 levels became more invasive and that this invasion was reverted by removing cilia.”
High levels of SAS-6 make cells grow more cilia – hair-like structures that stick out from the surface and act like sensors.
The study in Life Science Alliance shows these extra cilia activate the YAP/TAZ, signalling pathway that drives tumour growth and spread.
The team investigated what happens when cells produce a version of SAS-6 that doesn’t break down.
They found the cells grew longer cilia, moved more and noticeably changed shape – becoming flatter and more flexible – all signs of an invasive cell.
When scientists blocked the YAP pathway or removed the cilia, the cancer invasion ‘reduced to almost negligible levels’.
They then found the same pattern in a real lung cancer cell line, which has high levels of SAS-6. Removing SAS-6 in this patient-derived cell line reverted invasion and YAP pathway activation.
Because several human cancers have unusually high levels of SAS-6, the protein could potentially be used as a marker for metastatic cancer. Understanding how SAS-6 and cilia drive cancer cell invasion could also help design novel therapies based on cilia specific signalling pathways.
“We think this gives us a new way to understand how cellular signals control cancer spread,” said Dr Tanos. “It could lead to smarter therapies and better ways to predict which cancers will turn aggressive.”
Source
Dysregulated SASS6 expression promotes increased ciliogenesis and cell invasion phenotypes published in
Life Science Alliance
