Pune: In biology textbooks, the Golgi apparatus is often depicted as a stack of flattened sacs—the cell’s ‘post office’ that receives, processes, and ships proteins and lipids. However, a groundbreaking study by researchers at the Indian Institute of Science Education and Research (IISER) Pune reveals that this often-overlooked structure does much more: it responds directly to the physical environment of a tumour and helps determine how aggressively cancer spreads.The study, published recently in the Journal of Cell Science, demonstrates that breast cancer cells can “feel” the stiffness of their surroundings and reorganize their internal machinery accordingly.“As breast cancer develops, the tissue around a tumour, extracellular matrix—gradually becomes stiffer, moving from a sponge-like consistency to something more like rubber,” said Nagaraj Balasubramanian, professor at IISER Pune. “This stiffening isn’t just a side effect; it actively helps cancer spread. We discovered a previously unknown connection between this increased stiffness and structural changes in the Golgi apparatus. This helps explain how cancer cells sense and respond to their environment, influencing how they grow and migrate.”Over a five-year period, a research team led by PhD student Arnav Saha and undergraduate Tushar Sherkhane, under Balasubramanian’s supervision, studied two types of breast cancer cells: the highly invasive MDA-MB-231 and the less aggressive MCF7.The researchers observed that because the Golgi acts as the cell’s packaging and distribution centre, changes in its shape directly impact how proteins are handled, which in turn dictates cell behaviour.“In highly invasive breast cancer cells, we found that as the surrounding material became stiffer, the Golgi apparatus became more tightly packed and better organised. Simultaneously, these cells spread out more, a behavior linked to their ability to invade other tissues,” said Balasubramanian. “In contrast, the less aggressive MCF7 cells showed a scattered and disorganised Golgi regardless of environmental stiffness, even though they also spread more on stiffer surfaces.“The team identified a specific signalling pathway—AXL → Arf1 → Golgi — that plays a crucial role in this process.“Imagine the extracellular matrix as the ground a cell stands on. When it stiffens, it’s like walking on concrete instead of soft soil. The cell needs a way to sense this change,” Balasubramanian said. “That’s where the protein AXL comes in; it acts as a sensor. Once AXL detects stiffness, it signals through another protein, Arf1, which sits at the Golgi and regulates its organisation. When we blocked AXL in invasive cells, the Golgi no longer reorganised in response to stiffness. Conversely, when we introduced AXL into less aggressive cells, their Golgi began responding to the stiffness.”While most current cancer drugs target genes or growth signals, this study suggests that the physical properties of a tumour are also a major driver of the disease — and a potential target for treatment.When asked if disrupting Golgi reorganisation by blocking AXL could prevent cancer spread, Balasubramanian said, “The Golgi could be an attractive candidate for targeting to reverse cancer growth. XL, as a regulator of the Golgi’s response to matrix stiffness, is also a strong candidate. Our ongoing studies are exploring how targeting AXL, both at the Golgi and elsewhere in the cell, could help regulate cancer progression.”
