Institute scientist finds breakthrough for liver cancer promotion

Dr. Ningling Kang, head of the Tumor Microenvironment and Metastasis lab at The Hormel Institute UMN, published a discovery describing how a particular protein, diaphanous homolog 1 (Diaph1), turns normal liver cells into cancer-promoting cells.

“Protein diaphanous homolog 1 (Diaph1) promotes myofibroblastic activation of hepatic stellate cells by regulating Rab5a activity and TGFβ receptor endocytosis” was published in The FASEB Journal. Multiple researchers from Dr. Kang’s lab at The Hormel Institute worked together to make this discovery.

“Hepatic stellate cells create a microenvironment that helps cancer cells to implant and grow in the liver,” said Kang, who joined The Hormel Institute in 2013 coming from Mayo Clinic. “This discovery is important because it supports Diaph1 as a potential target to block cancer/liver communications and liver metastasis – it helps us as we seek to find how to prevent and stop cancer from progressing.”

Cancer that originates from the colon, pancreas, or breast can spread into the liver. This process is called metastasis. In the liver, cancer cells communicate with the cells that normally live in the liver, cells called hepatic stellate cells. The cancer cells can transform the hepatic stellate cells into metastasis-promoting myofibroblasts. These myofibroblasts make the liver a more welcoming place for metastatic cancer.

The newly published study by Kang and her lab reveals that a protein called diaphanous homolog 1 (Diaph1) promotes the transformation of hepatic stellate cells into myofibroblasts by regulating the function of TGFβ receptor 2 and TGFβ signaling of hepatic stellate cells.

For their next step, Kang and her lab will test if an inhibitor targeting Diaph1 is effective at preventing and suppressing liver metastasis of colorectal cancer in mice, and hopefully, in cancer patients in the future. Metastatic cancers can be much more difficult to treat than cancers that have not spread to other parts of the body. This is why research like Dr. Kang’s is so important, to find new ideas for how to treat metastatic cancers.

Another of Dr. Kang’s papers, “p300 Acetyltransferase Is a Cytoplasm-to-Nucleus Shuttle for SMAD2/3 and TAZ Nuclear Transport in Transforming Growth Factor β-Stimulated Hepatic Stellate Cells”, published in Hepatology, was just named the top downloaded paper of 2018-2019, making it one of the most widely read papers in the high impact journal.