Compared to other types of breast cancer, triple negative breast cancers are often more aggressive and have fewer treatment options. In a new study published in the journal Proceedings of the National Academy of Sciences (PNAS), researchers from the University of Utah have identified a molecular mechanism that triple negative breast cancer cells use to survive and grow.
The team explain that many cancer cells, including triple negative cells, are addicted to the sugar glucose and the amino acid glutamine. Normal cells use glucose and glutamine but cancer cells use them at a very elevated rate and they actually become addicted to these nutrients and they are required for their growth.
The researchers found that two proteins, one called Myc, the other called thirodoxin-interacting protein, or TXNIP, normally work in opposition to each other in cells in culture. Myc helps cancer cells take up and use glucose so they can grow and survive, while TXNIP blocks glucose uptake, limiting the growth-inducing functions of Myc. By contrast, in triple negative breast cancer cells, the researchers discovered that Myc reduces the expression of TXNIP. This increases glucose uptake, which supports the growth-inducing functions of Myc.
The data findings suggest that high levels of Myc and low levels of TXNIP promote triple negative breast cancer cell growth and survival. Corroborating this finding, high levels of Myc combined with low levels of TXNIP correlate with poor patient outcome when examined in large clinical datasets. Further, the relationship between Myc and TXNIP is not observed in other types of breast cancer, suggesting that it is a feature of only aggressive triple negative breast cancers and not other less aggressive breast cancer types.
The team state that it may be possible to exploit this vulnerability in triple negative breast cancer. From a therapeutic standpoint researchers could theorise that the cells that are addicted to these nutrients could be starved and killed more easily than normal cells.
While this current study primarily focused on the role of Myc and TXNIP in triple negative cancer nutrient uptake and utilization, the researchers state that the proteins also appear to play a role in metastasis, the process by which cancer cells spread to other parts of the body. What the team discovered was that if tumours are taken from relatively young women, under age 53 with stage 1 or stage 2 breast cancer, and they have a high Myc, low TXNIP gene signature, these patients are more likely to have secondary metastasis later in life. The team surmise that this signature may be an early marker for metastatic disease.
If this result is validated in clinical trials, the team state that looking for the high Myc, low TXNIP signature will identify women at high risk for recurrence who could then be treated more aggressively and watched more closely.