By Daniel Walocha ‘19

CD133 is a biomarker for cancer stem cells (CSC) in esophageal squamous cell carcinomas (ESCC). Cancer cells have remarkable resistance to drugs and therapies, so discovering a potential therapeutic target to make the CSCs in ESCC more susceptible to treatment is of particular interest. Dr. Wen Xu et al. from Columbia University looked to elucidate the pathway for CD133 and associated markers in CSC.

The research group utilized in vitro cell culture models to discover part of the pathway for CD133, a glycoprotein highly expressed in cancer cells as shown in previous experiments. The glycoprotein is proposed to organize the cell member topology, and the research group discovered that knockout of insulin-like growth factor 2 (IGF-2). IGF-2 functions similarly to insulin and has mitogenic activities in promoting CSC growth in ESCC. The researchers used immunoprecipitation to see the interaction as well as a marked increase in caspase activity via western blot following IGF2 knockout.

The same phenotypic effect was found in treatment with P13K/AKT inhibitors that prevent the same pathway from occurring downstream of CD133 activation. The researchers further established that ESCC has correlated, increased expression level of IGF2 and CD133. Case studies displayed a similar correlation, associated with poor prognosis. In vivo studies with mice found that treating IGF2 with a neutralizing antibody has made tumor xenografts more vulnerable to 5-fluorouracil chemotherapy treatment.

The importance of this interaction provides precedent for future research in elaborating the IGF-2/CD133/P13K/AKT pathway. Researchers should look into other potential protein interactions within the same pathway, starting with already confirmed signaling molecules.

References:

1. W. Wen, et al., IGF2 induces CD133 expression in esophageal cancer cells to promote cancer stemness. Cancer Letters 1-10 (2018). doi: j.canlet.2018.03.039.
2. Image retrieved from: https://en.wikipedia.org/wiki/Breast_cancer