Despite recent progress in colorectal cancer screening and treatment, metastatic colorectal cancer remains a leading cause of cancer death worldwide. The molecular mechanisms that enable cancer cells to metastasize are poorly understood, although emerging evidence indicates that transcriptional networks required for stem cell properties during embryogenesis are co-opted during metastatic progression. Recent studies identified HMGA1 as a key transcription factor enriched in human embryonic stem cells, hematopoietic stem cells, refractory leukemia and high-grade/poorly differentiated cancers from the breast, brain, and bladder. Moreover, tumors overexpressing HMGA1 and eight other ES transcription factor genes had decreased survival, underscoring the importance of these genes in tumor progression. More recently, we found that HMGA1 protein levels correlate with poor differentiation status and (R)Ginsenoside-Rg3 decreased survival in pancreatic cancer, further implicating HMGA1 in an undifferentiated, stem-like state and tumor progression. The HMGA1 gene encodes the HMGA1a and HMGA1b chromatin remodeling proteins, which function to modulate gene expression by altering chromatin structure and assembling transcription factor complexes at specific promoters. Previous studies demonstrate that HMGA1 induces oncogenic properties in cultured cells and causes aggressive tumors in transgenic mice. The precise molecular pathways regulated by HMGA1 in transformation, however, are only beginning to emerge and studies to elucidate HMGA1 transcriptional networks are likely to uncover fundamental pathways involved in tumor progression and development. Here, we report for the first time that the HMGA1 drives proliferative changes and polyp formation in the intestines of transgenic mice and directs molecular pathways important in tumor progression and stem cell properties in human colon cancer cells. Taken together, these findings suggest that HMGA1 promotes tumor progression in colon cancer by reprogramming colonic epithelium to a stem-like state. Metastatic colon cancer is highly lethal and the incidence is rising, particularly in younger individuals. Current therapies are limited by the emergence of metastatic cancer cells that are resistant to treatment. Recent evidence suggests that these refractory cells develop because they co-opt the cellular networks involved in embryonic development and (R)Ginsenoside-Rh1 become capable of metastasizing and evading therapy. We also discovered that HMGA1 is required for metastatic progression to the liver in vivo. Notably, several recent studies have also shown that HMGA1 is enriched in normal stem cells, including embryonic and hematopoietic stem cells, in addition to poorly differentiated, or refractory stem-like cancers, suggesting that HMGA1 helps to drive a stem-like state, both in normal development and cancer. HMGA1 is also highly expressed during embryogenesis, with low or undetectable expression in most differentiated, adult tissues. In summary, our studies provide the first evidence linking HMGA1 to cellular properties and transcriptional networks important in stem cells, EMT, and metastatic progression in colon cancer. Although further work is needed, these results underscore the role of HMGA1 as a key regulator in tumor progression and a stem-like state in colon cancer and suggest that targeting HMGA1 pathways could be beneficial in therapy for colon cancer. Because HMGA1 is enriched in embryonic stem cells, tissue-specific stem cells, and virtually all aggressive tumors studied to date, our findings are likely to relevant not only to diverse human cancers, but also to normal development. Pesticides are a common source of pollution, being present at a large scale in many European soils. Pesticides are designed to affect a certain class of organisms but they also affect non-target organisms.