Table 1.
Table summarizing the CIN-causing mitotic phenotypes observed in different cell types and/or models upon de-regulated oncogenic signaling.
Pathway | Gene(s) | Mitotic phenotype | Model | Reference |
---|---|---|---|---|
RB | E2F | Chromatin assembly/condensation; chromosome mis-segregation; impaired SAC; stabilization of k-MT attachments | Human fibroblasts (WI-38), MEFs, HCT116, T24, HT1197, SW480, U2OS, IMR-90, RPE1, NIH-3T3 | Ren et al. (2002), Hernando et al. (2004), Kabeche and Compton (2012) |
RB | Chromosome condensation; impaired centromere structure; heterochromatin structure; chromosome mis-segregation | MEFs; RPE1; Drosophila neuroblasts | Isaac et al. (2006), Coschi et al. (2010), Manning et al. (2010) | |
RB, p107, p130 | Chromatid breaks; cohesion defects | MEFs | Manning et al. (2010), van Harn et al. (2010) | |
Wnt | Conductin/AXIN2 and APC | Premature centrosome separation (Plk1-dependent); Impaired SAC (Plk1-dependent) | MEFs; SW480, U2OS, HCT116, DLD1, HEK293T, HeLa | Hadjihannas et al. (2006), Hadjihannas et al. (2010), Ruan et al. (2012) |
Disheveled 2 (Dvl2) | Regulation of MT-plus-ends (Plk1-dependent); Impaired SAC (Mps1, Bub1, and BubR1-dependent) | HeLaS3, U2OS | Kikuchi et al. (2010) | |
GSK3β | Mis-alignment; chromosome mis-segregation; micronuclei formation | HeLa, HEK293T, Drosophila embryos | Wakefield et al. (2003), Bobinnec et al. (2006), Tighe et al. (2007) | |
β-catenin | Loss of centrosome separation; monopolar spindle formation; chromosome condensation | HeLa, HEK293T, NIH-3T3, MDCK, U2OS, DlD1, HCT116 | Kaplan et al. (2004), Bahmanyar et al. (2008), Davalos et al. (2012) | |
APC | Hyper-stabilization of k-MT attachment | Mouse ES cells, Ptk2, HT29, SW480, Caco2, LoVo, HCT116, RKO, HEK293T, HeLa, RPE1 | Fodde et al. (2001), Zumbrunn et al. (2001), Green and Kaplan (2003), Green et al. (2005), Draviam et al. (2006), Bakhoum et al. (2009a) | |
DNA damage | p53 | Centrosome function (Aurora A, Plk2, and Plk4-dependent) | Mouse hepatocytes | Kurinna et al. (2013) |
unknown component | Centrosome integrity; multipolarity; chromosome mis-segregation | CHO | Hut et al. (2003) | |
Chk1 | k-MT stability (Aurora B-dependent); Centrosome amplification; Disrupted SAC function (Mad2, BubR1, and Aurora B-dependent) | DT40, HCT116, HEK293T, U2OS, mouse MECs, HC11, NIH-3T3, HeLa, OVCAR-8, OVCA-432, A2780, OVCAR-5 | Bourke et al. (2007), Zachos et al. (2007), Carrassa et al. (2009), Peddibhotla et al. (2009), Chila et al. (2013) | |
Chk2/BRCA1 | Abnormal mitotic spindle assembly; lagging chromosomes | HCT116, HeLa, BJ-hTERT | Stolz et al. (2010b) | |
DNA-PKcs | Abnormal spindle formation | HeLa, AT5BIVA | Shang et al. (2010) | |
Ras | HRas | Weakened SAC | PCCL3 | Knauf et al. (2006) |
KRas | Chromosome mis-segregation | DLD1, HCT116 | Luo et al. (2009) | |
BRAF | Impaired SAC (Mps1-dependent); supernumerary centrosomes | SK-MEL-5, SK-MEL-28, A375, SBcl2, hTERT-HME | Cui et al. (2010) | |
Notch | Notch | Mitotic delay (CycB1-dependent) | KS-IMM, KS-Y1 | Curry et al. (2007) |
TGF-β | Ski | Weakened SAC function; lagging chromosomes/chromosome bridges; micronuclei formation | Primary MEFs, SV-40 immortalized MEFs | Marcelain et al. (2012) |
Smad2/3 | Impaired SAC function? | Sw480, HeLa | Zhu et al. (2007) | |
NF-κB | IκB | Centrosome function (Aurora A-dependent); Mitotic arrest (CycB1 and Plk1-dependent); chromosome mis-segregation | HeLa, COS7, Primary MEFs | Prajapati et al. (2006), Irelan et al. (2007) |
Integrin | ILK | Centrosome clustering (TACC3 and ch-TOG-dependent); Hyper-stabilization of k-MT dynamics | BT549, MDA-MB-231, MCF7, MCF10A, 184-hTERT, PC3, DU145, BPH-1, HEK293T, HeLa, IMR-90 | Fielding et al. (2008), Fielding et al. (2011), Lim et al. (2013) |
Hippo | NDR1/Fry/MST2 | Chromosome misalignment | HeLa | Chiba et al. (2009) |
MST1 | Centrosome overduplication; Stabilization of k-MT attachments (Aurora B-dependent) | HeLa, U2OS, PT67, COS7, RPE1 | Hergovich et al. (2009), Oh et al. (2010) | |
LATS2 | Centrosome fragmentation; chromosome misalignment; loss of SAC activity; cytokinesis failure | Primary MEFs | Yabuta et al. (2007) | |
KIBRA | Defects in mitotic spindle formation; chromosome misalignment | HEK293T, MCF7, HeLa | Zhang et al. (2012) |