Table 2.
Dysregulation in the expression of CDKs and their regulatory cyclin subunits in various cancers
| Alteration | Type of cancer | Reference(s) |
|---|---|---|
| Cyclin A | ||
| Amplification | BC | Husdal et al. (2006) |
| Overexpression | CRC, EC, TC, HCC, Soft tissue sarcoma, AML, ESCC | Ekberg et al. (2005), Nar et al. (2012), Wang et al. (1996), Furihata et al. (1996), Huuhtanen et al. (1999), Chao et al. (1998), Santala et al. (2014) and Li et al. (2002) |
| Truncated form owing to the integration of HBV DNA | HCC | Chao et al. (1998) and Wang et al. (1990) |
| Cyclin B | ||
| Overexpression | BC, GC, ESCC, NSCLC, TC | Nar et al. (2012), Aaltonen et al. (2009), Begnami et al. (2010), Murakami et al. (1999) and Soria et al. (2000) |
| Overexpression/nuclear localization | BC | Suzuki et al. (2007) |
| Cyclin D | ||
| Amplification/overexpression | HNSCC | Akervall et al. (1997), Meredith et al. (1995) and Michalides et al. (1997) |
| Overexpression | EC, LC, PaC, Follicular MCL, BC, HNSCC, ESCC, CRC, OC, GC | Dobashi et al. (2004), Gansauge et al. (1997), Kim and Diehl (2009), Seong et al. (1999), Barbieri et al. (2004), Shan et al. (2017), Moreno-Bueno et al. (2004) |
| IgH translocation and overexpression | MCL, MM | Bertoni et al. (2006), Li et al. (1999), Bergsagel and Kuehl (2005) and Chesi et al. (1996) |
| Truncated form (cyclin D1b) (A870G polymorphism) | PC, BC, NSCLC, ESCC, PC | Comstock et al. (2009), Millar et al. (2009), Gautschi et al. (2007), Betticher et al. (1995), Li et al. (2008), Knudsen et al. (2006) and Burd et al. (2006) |
| Truncated cyclin D1b and co-expression with cyclin D1a | BC | Abramson et al. (2010) |
| Cyclin D1a isoformsa | MCL | Wiestner et al. (2007) |
| Mutation disrupting phosphorylation-dependent nuclear export | ESCC | Benzeno et al. (2006) |
| Cyclin E | ||
| Amplification | OC | Nakayama et al. (2010) and Karst et al. (2014) |
| Overexpression/amplification | CRC, BC | Wang et al. (1996), Kitahara et al. (1995) and Scaltriti et al. (2011) |
| Overexpression | Osteosarcoma, NSCLC, PaC, BC, CRC, Acute and chronic leukemias, HL, NHL, IBC | Lockwood et al. (2011), Koutsami et al. (2006), Yue and Jiang (2005), Erlanson et al. (1998), Wołowiec et al. (1995), Lindahl et al. (2004), Zhou et al. (2011), Alexander et al. (2017) |
| Overexpression/high nuclear expression | Early development of BC | Shaye et al. (2009) |
| Overexpression of small isoforms | BC | Keyomarsi et al. (1995), Porter and Keyomarsi (2000), Weroha et al. (2010) and Wingate et al. (2009) |
| LMV isoform (truncated) | BC, OC, melanoma | Harwell et al. (2004), Akli and Keyomarsi (2004), Bedrosian et al. (2004) and Bales et al. (2005) |
| CDK1 | ||
| Overexpression | Advanced melanoma, B cell lymphoma, CRC, ESCC | Zhao et al. (2009), Abdullah et al. (2011), Li et al. (2020) and Zhang et al. (2021b) |
| CDK2 | ||
| Overexpression | Oral cancer, advanced melanoma, BC, LSCC | Wang et al. (1996), Abdullah et al. (2011), Weroha et al. (2010), Mihara et al. (2001) and Georgieva et al. (2001) |
| CDK3 | ||
| Overexpression | Glioblastoma | Zheng et al. (2008) |
| Highly expressed | Non-malignant BC | Cao et al. 2017) |
| CDK4 | ||
| Amplification | Glioblastoma, refractory rhabdomyosarcoma, osteosarcoma | Park et al. (2014), Wei et al. (1999) and Schmidt et al. (1994) |
| Amplification/overexpression | Sporadic BC, uterine cervix cancer, osteosarcoma | Wei et al. (1999), Wunder et al. (1999) and Cheung et al. (2001) |
| Overexpression | LC, melanomas | Dobashi et al. (2004), Wu et al. (2011) and Smalley et al. (2008) |
| R24C mutation | MCL, LC, familial melanoma | Sotillo et al. (2001), Sotillo et al. (2005), Chawla et al. (2010), Puyol et al. (2010), Vincent-Fabert et al. (2012), Zuo et al. (1996), Wölfel et al. (1995), Vidwans et al. (2011), Tsao et al. (2012) and Sheppard and McArthur (2013) |
| CDK5 | ||
| Amplification/overexpression | PaC | Eggers et al. (2011) |
| Overexpression | PC | Strock et al. (2006) |
| BC | Liang et al. (2013) | |
| mRNA up-regulation | BC, CRC, HNSCC, OC, LC, lymphoma, PC, MM, sarcoma, bladder cancer | Levacque et al. (2012) |
| SNPs in the promoter region | Enhanced risk of LC | Choi et al. (2009) |
| Reduced methylation of promoter leading to overexpression | MCL | Leshchenko et al. (2010) |
| CDK6 | ||
| Amplification | SCC, glioma, lymphoma | Costello et al. (1997) and Chilosi et al. (1998) |
| BC | Yang et al. (2017) | |
| Overexpression | Medulloblastoma | Mendrzyk et al. (2005) |
| Highly expressed | NSCLC | Gong et al. (2020) |
| Sumoylation | Glioblastoma | Bellail et al. (2014) |
| Translocation | Splenic marginal zone lymphoma | Corcoran et al. (1999) |
| D32Y mutation | Neuroblastoma | Easton et al. (1998) |
| CDK7 | ||
| Overexpression | HCC, OSCC, osteosarcoma | Liu et al. (2018), Jiang et al. (2019) and Ma et al. (2021) |
| CDK8 | ||
| Amplification | BC | Broude et al. (2015) |
| Amplification and overexpression | CRC | Firestein et al. (2008), Firestein et al. (2010) and Seo et al. (2010) |
| Overexpression | Colon cancer, GC | Adler et al. (2012) and Kim et al. (2011) |
| Tumor-suppressive function | EC | Gu et al. (2013) |
| siRNA-mediated silencing inhibits proliferation | BC | Li et al. (2014) |
| Up-regulation upon loss of macroH2A histone variant | Melanoma | Kapoor et al. (2010) |
| CDK8 expression and the delocalization of β-catenin expressionb | GC | Kim et al. (2011) |
| CDK9 | ||
| Overexpression | PaC, EC | Kretz et al. (2017) and He et al. (2020) |
| Highly expressed | CLL, MM | Tong et al. (2010) |
| High expression predicts poor prognosis | Osteosarcoma | Ma et al. (2019) |
| Differential expression correlating with malignant transformation | Lymphoma | Bellan et al. (2004) |
| Expression correlates with differentiation grade | Primary neuroectodermal tumors and neuroblastoma | Falco et al. (2005) |
| CDK10 | ||
| Down-regulation | HCC, biliary tract cancer, GC | Zhong et al. (2012), Yu et al. (2012) and You et al. (2018) |
| Low expression | GC | Zhao et al. (2017) |
| CDK11 | ||
| Overexpression | Osteosarcoma | Duan et al. (2012) |
| Gene deletion/translocation | Neuroblastoma | Lahti et al. (1994) |
| Loss of one allele of Cdc2L/decreased CDK11 expression | Melanoma | Chandramouli et al. (2007) |
| CDK12 | ||
| Overexpression | BC, cervical cancer | Paculová and Kohoutek (2017), Yang et al. (2021a) |
| CDK13 | ||
| Up-regulation | PC | Qi et al. (2021) |
| CDK14 | ||
| Overexpression | ESSC, HCC, NSCLC | Miyagaki et al. (2012), Leung et al. (2011) and Yang et al. (2021b) |
| Highly expressed | CRC | Mao et al. (2017) |
| CDK15 | ||
| Highly expressed | CRC | Huang et al. (2022) |
| Up-regulation | BC | Zhang et al. (2021c) |
| CDK16 | ||
| Overexpression | NSCLC, CSCC | Wang et al. (2018) and Yanagi et al. (2017) |
| CDK19 | ||
| Amplification | BC | Broude et al. (2015) |
| Overexpression | Advanced PC | Brägelmann et al. (2017) |
| Up-regulation | HCC | Cai et al. (2021) |
| CDK20 | ||
| Overexpression | LC | Wang et al. (2017) |
HBV, hepatitis B virus; HCC, hepatocellular carcinoma; AML, acute myeloid leukemia; ESCC, esophageal squamous cell carcinoma; NSCLC, non-small cell lung cancer; MCL, mantle cell lymphoma; MM, multiple myeloma; CRC, colorectal cancer; SCC, squamous cell carcinoma; TC, thyroid carcinoma; BC, breast cancer; IBC, inflammatory breast cancer; GC, gastric cancer; HNSCC, head and neck squamous cell carcinoma; OSCC, oral squamous cell carcinoma; LC, lung cancer; PaC, pancreatic carcinoma; OC, ovarian carcinoma; CSCC, cutaneous squamous cell carcinoma; PC, prostate cancer; EC, endometrial cancer; HL, Hodgkin's lymphoma; NHL, non-Hodgkin's lymphoma; LSCC, laryngeal squamous cell cancer; CLL, chronic lymphocytic leukemia; IgH, immunoglobulin heavy chain; UTRs, untranslated regions; LMV, low molecular weight; SNPs, single nucleotide polymorphisms
aHaving truncated 3′ UTRs, not alternatively spliced cyclin D1b mRNA isoforms/changes of the 3′ UTR structure of the cyclin D1 gene (CCND1)
bPositively correlate with carcinogenesis and tumor progression