Scientists crack pathway that makes brain tumour aggressive

IISc, NIMHANS finding on protein regulation published in the journal Neuro-Oncology.

In just a few decades, medicine has made great strides in battling cancer. But the road to understanding the disease — that ‘emperor of maladies’— has still not been mapped. Take, for instance, glioblastoma, one of the more common brain tumours. When it is most aggressive, it can reduce a patient’s life to a little over a year despite treatment.

While a cure is still a long way off, scientists at the Indian Institute of Science (IISc) and the National Institute of Mental Health and Neurosciences (Nimhans) have found the pathway that makes the tumour cells more aggressive.

The team’s study, published in a recent issue of the journal

Neuro-Oncology , explains how IGFBP-2 (insulin-like growth factor binding protein 2), one of the proteins present in the extracellular fluids surrounding the cells, makes the tumour aggressive. While previous studies have shown that patients with more aggressive forms of glioblastoma had higher IGFBP-2 levels in their serum, the IISc-NIMHANS study reveals that the IGFBP-2 uses the protein beta-catenin as its pathway.

Beta-catenin’s role

“IGFBP-2 makes the tumour aggressive by regulating the beta-catenin, which is shown to be very important for making tumour aggressive,” said Paturu Kondaiah, Professor, Department of Molecular Reproduction Development and Genetics, IISc, and the lead member of the study.

In glioblastoma cells with high levels of IGFBP-2 expression, nuclear beta-catenin levels were higher. In cells that made very little or no IGFBP-2, nuclear beta-catenin levels were low.

Unlike IGFBP-2, which is present outside the cell, beta-catenin can shuttle in and out of the nucleus of the cell. When present inside, it influences protein production.

The researchers found that higher IGFBP-2 levels led to inactivation of another protein — GSK3, which impairs the degradation of beta-catenin inside the cell. Hence, beta-catenin can easily travel to the nucleus and induce production of new proteins that instruct the tumour cells to proliferate faster than normal, and start invading other tissues, an IISc release explained.

The researchers are now working on further delineation of the pathway and other players involved in IGFBP-2-mediated tumour promotion. But inhibiting IGFBP-2 could be a good therapeutic strategy, Prof. Kondiah said.