LIN28B promotes colorectal cancer differentiation and metastasis

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second most common cause of cancer deaths in the United States. Despite recent advances in treatment, metastatic CRC remains difficult to treat and has poor prognosis, with the 4-year survival rate for stage 4 CRC being around 15%. Our research focuses on how LIN28B, a protein involved in cell growth and development, contributes to the spread of CRC. Our past studies have shown that high levels of LIN28B are linked to poor outcomes in human CRC patients, and it can promote both the initiation and spread of CRC. The goal of this proposed research is to study how LIN28B promotes the spread of CRC to other parts of the body. To explore this, we have three interrelated specific aims: 1) To investigate how LIN28B affects Claudin-1 (CLDN1), a protein that allows cancer cells to stick together and spread through the bloodstream, and how this contributes to the spread of CRC, 2) To determine how LIN28B allows CRC cells to leave the colon, invade into and survive in the bloodstream, and grow in the liver, and 3) To identify subpopulations of CRC cells that have a higher likelihood of spreading and determine how LIN28B affects their behavior. To achieve these aims, we will use special mouse models of CRC and genetically engineered human CRC cell lines. We will analyze these models using sequencing and other molecular techniques to understand how LIN28B affects the behavior of different groups of CRC cells. Ultimately, we hope to shed light on new targets for preventing CRC spread and to better understand the processes that allow cancer cells to migrate and colonize other parts of the body.