Establishing a biotin-based affinity sytem to uncover the role of LSF in immortalized human fetal hepatocytes
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Late SV40 Factor (LSF) is a ubiquitously expressed mammalian transcription factor and an oncogene in Hepatocellular Carcinoma (HCC), a deadly cancer that currently has poor treatment options. LSF is expressed at low levels in normal hepatocytes but is overexpressed in HCC making it a key target for treating HCC. Small molecule inhibitors called Factor Quinolinone Inhibitors (FQIs) that specifically target LSF have been developed as possible chemotherapeutics to treat HCC. FQI1, a lead inhibitor, reduces HCC tumor sizes in mouse models without any evident toxicity in other organs. The focus of many recent studies regarding LSF has been to characterize it as an oncogene in HCC, however little is known about how it functions in normal hepatocytes. Understanding the role of LSF in hepatocytes could provide more insight into how it drives HCC as well as give more insight into how to target it in HCC. Here, FQI1 was used as a tool to uncover phenotypes in immortalized fetal hepatocytes (FH-B) that result from inhibiting the low levels of LSF expressed in this cell line. Rapid morphological phenotypes resulting from FQI1 treatment suggested a disruption in a non-transcriptional v process, which was unexpected since LSF is a transcription factor. Further investigation revealed that LSF and a-tubulin interact in immortalized human fetal hepatocytes and that this interaction at least partially disrupted upon short treatment with FQI1 in FH-B cells. These findings suggest mechanisms for non-transcriptional roles that LSF may have in addition to its roles as a transcription factor.