WHY PHYSICAL PRESSURE MAY HELP BREAST CANCER CELLS GROW

New research reveals how mechanical forces inside tumours can fuel aggressive breast cancer behaviour, opening the door to potential new treatment approaches.

Scientists have uncovered a surprising reason why some breast cancers grow and spread more aggressively than others.

According to new research led by the University of Adelaide, intense physical pressure experienced by early cancer cells in cramped tissue spaces may actually help them thrive.

Published in Science Advances, the study shows that rather than slowing tumour growth, this mechanical “squeeze” can activate biological processes that allow cancer cells to multiply faster and become more invasive.

How pressure influences breast cancer growth

As tumours begin to form, cancer cells often expand within restricted areas such as the milk ducts of the breast. This creates significant physical pressure, which researchers have now found can trigger powerful survival mechanisms within the cells.

Lead researcher Professor Michael Samuel from Adelaide University’s Centre for Cancer Biology and the Basil Hetzel Institute said breast cancer cells can exploit a sensor normally used by the body to perceive touch.

“This process leaves a lasting ‘mechanical memory’ in breast cancer cells, continuing to promote aggressive behaviour long after the pressure itself has been relieved,” Professor Samuel said.

“Solid tumours experience intense physical pressure at early stages of the disease, as cancer cells multiply within space-restricted tissues, such as the milk ducts of the breast.

Until now, it has been unclear how cancer cells sense this pressure and whether it influences how the disease progresses.

“We tend to think about cancer as a genetic disease, but this work shows that physical forces inside tumours are just as important as cancer-causing genetic changes.”

The science behind the ‘mechanical memory’

Researchers found that cancer cells detect pressure through a molecule known as PIEZO1. This channel connects the inside of the cell to its external environment and, when activated by pressure, allows calcium ions to flow into the cell.

This sets off a chain reaction involving the Rho ROCK pathway, which regulates cell movement, shape and growth. In laboratory models, even brief periods of compression were enough to significantly increase tumour size and accelerate cancer cell division.

Beyond stimulating growth, mechanical pressure was also found to push cancer cells towards a more aggressive and invasive state through a biological process called epithelial-mesenchymal transition.

Co-lead author Dr Sarah Boyle said the long-lasting impact of pressure on cancer behaviour was one of the study’s most striking findings.

"Even fairly brief periods of pressure can cause mechanical memory by changing how DNA is packaged inside the cell, through chemical modifications to histone proteins,” Dr Boyle said.

“These modifications, referred to as epigenetic changes, alter how the DNA code is interpreted by the cell, allowing certain genes that drive tumour growth and aggressiveness to be switched on.”

Potential implications for future treatments

Importantly, the research found that PIEZO1 is more abundant in human breast cancers than in normal tissue, and higher levels are associated with poorer patient survival.

Blocking either PIEZO1 or the Rho ROCK pathway with specific drugs prevented compression from driving cancer aggressiveness in experimental models.

The findings suggest that targeting how cancer cells sense and respond to mechanical pressure could become a new strategy in early intervention and treatment.

“As cancers are increasingly recognised as mechanically responsive diseases, this work opens the door to a new area of ‘mechanotherapy’ treatments designed to interfere with the mechanical signals that tumours rely on to grow and spread,” Professor Samuel said.

Researchers believe this emerging field could also help identify patients at greater risk of developing aggressive breast cancers, based on pressure-sensing activity within tumours.