Researchers in Jun-Lin Guan’s lab in UC’s Department of Cancer Biology found a potential combination treatment target for breast cancer cells and breast cancer stem cells. 

Kanakaraju Manupati, PhD, postdoctoral fellow in Guan’s lab, researched a protein called NuMA1.

The protein is known to be upregulated in breast cancer, but the specific role it plays within tumours of breast cancer subtypes was not well-defined. 

Manupati’s research found that when NuMA1 was deleted in animal models of three different breast cancer cell lines, it reduced tumour growth.

Removing NuMA1 from breast cancer stem cells led to reduced metastasis, or cancer spread, suggesting it plays a role in cancer growth and spread in both breast cancer bulk and stem cells. 

“The interesting finding is that we observed that NuMA1 depicted various roles in different subtypes of breast cancer,” he said. 

There are currently no drugs that directly target NuMA1, but it is regulated by an enzyme called PIM1. The research team tested the effectiveness of a drug that blocks PIM1 and found the enzyme inhibitor reduced tumour formation and cancer spread in all three subtypes of breast cancer they tested.  

The treatment was even more effective when combined with an autophagy inhibitor that blocks the cell's process of breaking down nutrients to grow and thrive. 

“When we used this combination approach, we could see there is a significant reduction of breast cancer tumour formation as well as metastasis,” Manupati said.  

The knowledge that NuMA1 plays a role in both bulk breast cancer cells and breast cancer stem cells makes it a promising potential target, Manupati said. 

“To prevent breast cancer metastasis, we need to kill both breast cancer cells as well as breast cancer stem cells,” he said. “Therefore, we need to target both of these populations to fully prevent breast cancer.” 

Moving forward, Manupati said the team hopes to continue studying the potential applications of the therapy approach of using a combination of PIM1 and autophagy inhibitors and how NuMA1 works in a variety of breast cancer stem cells. 

Source: University of Cincinnati