Quantitative proteomic and phosphoproteomic comparison of human colon cancer DLD-1 cells differing in ploidy and chromosome stability

“…We hypothesized that this pathway might contribute to the increased TFEB activity in response to trisomy. This hypothesis is consistent with previous observations that constitutive trisomy activates the type I interferon pathway 11 , 21 , 22 . Recently, endogenous DNA damage and replication stress, which is also a hallmark of trisomic cells 3 , 13 , 19 , 20 , has been shown to cause accumulation of cytoplasmic DNA, thereby contributing to activation of the type I interferon pathway 23 , 25 , 26 , 41 .…”

“…Newly formed tetraploid cells inherit extra centrosomes that promote spindle multipolarity (Chen et al, 2016 ; Baudoin et al, 2020 ), which was proposed as the mechanism underlying the tumorigenic potential of tetraploid cells (Storchova and Pellman, 2004 ). In our 4N clones, however, a majority of cells formed bipolar spindles with a normal centrosome number, consistent with other reports (Ganem et al, 2009 ; Godinho et al, 2014 ; Kuznetsova et al, 2015 ; Potapova et al, 2016 ; Viganó et al, 2018 ) and recent evidence that extra centrosomes are quickly lost through asymmetric centrosome clustering during the evolution of tetraploid cells (Baudoin et al, 2020 ). Our findings suggest that rather than multipolarity resulting from extra centrosomes, relatively subtle variations in spindle geometry, spindle pole size, microtubule abundance, and cell volume can affect mitotic progression and SAC silencing in tetraploid cells.…”

“…During such bipolar divisions with asymmetric centrosome clustering, the chromosomes are partitioned in a bipolar manner and cytokinesis occurs at the midzone. Therefore, this process is unlikely to explain the size differences we observe in our clones, but it is consistent with the emergence of 4N cell populations in which the vast majority of cells assemble bipolar spindles with normal centrosome numbers (Ganem et al, 2009 ; Godinho et al, 2014 ; Kuznetsova et al, 2015 ; Potapova et al, 2016 ; Viganó et al, 2018 ; Baudoin et al, 2020 ).…”

“…The retention of DLD1-characteristic genetic variants in resistant phenotype, compared to their loss in the sensitive cell line, highlights the dynamic nature of cancer cell genomes. Similar observations in DLD1 cells were previously reported, demonstrating that genetic instability, combined with selective pressures such as drug exposure or prolonged culture, contributes to the retention or loss of specific alterations [ 47 , 48 ]. Both cell lines, namely DLD1 and DLD1-TxR, have been extensively utilized over many years in our previous studies.…”