In a breakthrough study conducted by scientists at the University of Sheffield, published on January 16, 2024, in PLOS Biology, breast cancer cells have been identified to exhibit a unique survival mechanism by consuming their surroundings when faced with nutrient scarcity.

The research sheds light on an undiscovered aspect of cancer cell survival and introduces a potential target for therapy development.

Breast cells, including tumor cells, reside within the Extracellular Matrix (ECM), a meshwork where nutrients are limited due to restricted blood flow, becoming scarcer as tumors grow.

The study, led by Dr Elena Rainero, focused on unraveling how tumor cells sustain growth in nutrient-deprived environments and obtain the raw materials necessary for their proliferation.

Dr Rainero explained, "This study identified a novel mechanism employed by breast cancer cells to survive in the challenging environment they are in within tumors

As sources of food are scarce, cancer cells gain the ability to eat and digest components of the matrix around them. We have identified a key metabolic process that the cells need to be able to take advantage of the matrix, which could represent a novel therapeutic target."

During the investigation, breast adenocarcinoma cells were seeded into different matrices, and the researchers observed that, when faced with nutrient deficiencies, tumor cells exhibited the ability to consume and digest components of the ECM.

The study revealed a metabolic process involving the breakdown of amino acids, particularly tyrosine and phenylalanine, which are essential for energy production.

Disrupting a central enzyme in this metabolic pathway, High Pressure Decorative Laminate (HPDL), significantly impaired cell growth. Additionally, inhibiting the macropinocytosis process and reducing the expression of HPDL and PAK1, a macropinocytosis promoter, hindered the tumor cells' migration and invasion.

Dr Rainero concluded, "Our results indicate that breast cancer cells take advantage of nutrients in the extracellular matrix in times of nutrient starvation, and that this process depends on both macropinocytosis and metabolic conversion of key amino acids to energy-releasing substrates."

Cancer Research UK, which funded the study, expressed optimism about the findings, acknowledging the potential for future treatments. Dr Anna Kinsella, Research Information Manager at Cancer Research UK, emphasized the importance of such research in laying the foundations for advancements in breast cancer treatment.