Identification of Spindle Regulators in Cancer and Cancer Stem Cells Division

During evolution, cells phenotypically change and optimize themselves to adapt to the different environment. This kind of phenomenon also happen in cancer evolution as a result of the heterogeneity within tumor. We were interested in the case of evolution of metastatic cancer, and we approached the question with a lung cancer cell line CL1-0 and it highly metastatic subline, CL1-5. Although CL1-5 has a smaller cell size, the spindle of the metastatic CL1-5 was longer than CL1-0, conflicting with the idea that spindle length should correlate with cell size. By transwell migration assay, we confirm that CL1-5 exists higher migration ability than CL1-0. Furthermore, to identify the key regulator involved, we employed microarray analysis and found that Kinesin-5, a microtubule regulator, was up-regulated in G2 phase CL1-5, and the near two-fold up-regulation was confirmed by RT-qPCR. To address whether Kinesin-5 play a role in metaphase spindle scaling in human cancer cells, we ectopically expressed Kinesin-5 in CL1-0 and found that metaphase spindle became CL1-5-like. Collectively, our data demonstrate that up-regulation of Kinesin-5 can lead to lengthened metaphase spindle. For the past few years, cancer stem cell (CSC), a population of cancer cells with stemness properties, took its place in the field of cancer evolution. We were also interested in how the expression of spindle regulators might be altered in CSCs. This was based on the reasoning that CSCs might be dysregulated in the balance of symmetric versus asymmetric cell division, in which spindle regulators might play a definitive role. By sphere-forming assay, we had successfully isolated colorectal CSCs from HCT116 and HT29 cell lines, and found escalated expression of Sox2, Oct4, Nanog and Lgr5, which are stemness-associated genes. Several spindle regulators also show different expression level between isolated CSCs and its parental cells. We will continue to compare the expression of spindle regulators in colorectal CSCs and non-CSCs, with the hope to identify key molecules whose dysregulation might lead to the most devastating aspect of cancer.