Galectin-1Promotes SAC Inactivation And Aneuploidy

Background: As a member of beta-galectoside binding proteins faminy, Galectin-1ishighly expressed in diverse tumor cells and tissues and correlated with tumor progressionand poor prognosis. Although it has been well defined that secreted Galectin-1plays animportant role in tumor proliferation, metastasis, immune escape and angiogenesis, thefunctions of intracellular molecules were complicated and paradoxical as reported invarious tumor types by different researches thus far. In this work, we try to illustrate theregulatory activity in mitosis and the intrinsic mechanism of tumor progression ofGalectin-1.Methods: Firstly, we detected the Galectin-1expression levels in synchronized HeLa cell;Then, FCM and BrdU Elisa were performed to determine the regulatory activity executedin M phase; Further, we discovered the specific Galectin-1targeting events in cell cycleby ICC and living cell time lapse images; Based on the previous results, we detailedlyexplained Galectin-1functions in metaphase-anaphase transition via Co-Ip and WB assays;At last, the aneuploidy-promoting property of Galectin-1has been assessed by ICC andkaryotype analysis.Results: Galectin-1was highly expressed in tumor cells when compared with normal control cells. The expression level of Galectin-1was stringently regulated throughout thecell cycle: the enrichment of Galectin-1was observed in M and G1phases, then itdeclined in S phase and reach the bottom at early G2phase. The re-accumulation arose inlate G2phase and thence there’s a cycle. Further bioinformatics analysis indentifiedNF-YB as the transcription factor that might regulate the fluctuation of Galectin-1. Ourdata also showed that Galectin-1significantly accelerated the metaphase-anaphasetransition in M phase by targeting SAC. It facilitated Mad2transport via Dynein-dependent manner. Thus, Galectin-1promoted Cdc20disassociated from MCC andactivated APC/C ubiquitin ligase, and the occurrence of chromosome lagging alsoelevated.Conclusion: The phenomena of Galectin-1inhibits SAC activity and promotesaneuploidy is consist with its high expression in tumor tissues. Therefore, our findingpresent an absolutely new profile of Galectin-1in tumor progression and expansion ofSAC-APC/C network.