A review on the role of cyclin dependent kinases in cancers

Ghafouri-Fard, Soudeh; Khoshbakht, Tayyebeh; Hussen, Bashdar Mahmud; Dong, Peixin; Gassler, Nikolaus; Taheri, Mohammad; Baniahmad, Aria; Dilmaghani, Nader Akbari

doi:10.1186/s12935-022-02747-z

Cancer Cell International

Table 1 Function of CDK1 based on cell line studies

From: A review on the role of cyclin dependent kinases in cancers

Tumor type	Targets/ Regulators and Signaling Pathways	Cell line	Function	References
Adrenocortical carcinoma	CENPF	SW13	CENPF/CDK1 signaling pathway was found to regulate the G2/M-phase, thus enhancing progression of adrenocortical carcinoma	[6]
Bladder cancer	PVT1/miR-31/CDK1 axis	RT4, T24, BIU‐87, and 5673	PVT1 facilitated proliferation, migration, and invasion via down-regulating miR-31 to enhance CDK1 expression	[7]
	TFCP2L1	Murine R1, E14TG2a, and gcOct4‐GFP ESCs, HBlEpC, J82, T24, 5637, HT1197, HT1376, and RT4	CDK1-mediated TFCP2L1 phosphorylation was found to have essential role in bladder cancer	[8]
	Cdc25C, Chk1, CDK1-cyclin B1 complex, Myt1, Wee1, phospho-Cdc25C (Ser216), Gadd45α, and 14-3-3 proteins	SCaBER, 5637, T24, UMUC3, TCCSUP, SV-HUC, T24, T24T, TCCSUP, UMUC1, and SV-HUC	Protein kinase D inhibitor “CRT0066101” suppressed expression of Cdc25C, which activates CDK1, but activated Chk1, that inhibits CDK1 and indirectly reduced the CDK1-cyclin B1 complex activity, so it inhibited bladder cancer growth by blocking cell cycle at G2/M	[9]
Breast cancer	KIAA1429	MCF-7, BT474, SUM1315, MDA-MB-231 and MCF-10A	KIAA1429 was found to positively regulate CDK1	[10]
	_	MCF-7 and MDA-MB-231	∆ CDK1: ↓ migration and invasion	[11]
	UBAP2L	MCF-7, ZR-75-30, BT-474, T-47D and MDA-MB-468, and MCF-10A	∆ UBAP2L: ↓ proliferation, colony formation, CDK1 levels, and ↑ cell cycle arrest	[12]
	miR-424	MDA-MB-231, HCC1937, MCF-10A, and HEK-293 T	↑↑ miR-424: ↓ proliferation and ↑ cell cycle arrest via targeting CDK1	[17]
	NUSAP1, and DLGAP5	MCF-7	∆ NUSAP1: ↓ proliferation, migration, and invasion via regulating CDK1 and DLGAP5 expression and ↑ sensitivity to E-ADM	[18]
	RBM7	SUM-1315, MCF-7, BT474, ZR-75-1, and MDA-MB-231	RBM7 was found to bind to the 3'-UTR of CDK1 transcript, which is involved in the stability of CDK1 mRNA RBM7 plays its oncogenic role by increasing the levels of CDK1	[19]
Burkitt lymphoma	miR-129 and iASPP	Raji and CA46	miR-129 was found to target CDK1, so it is involved in inhibiting iASPP phosphorylation and reducing proliferation ∆ CDK1: ↓ iASPP S84/S113 phosphorylation, so blocked iASPP nucleus localization	[13]
Cancer stem cells	RAS/MAPK/CDK1 pathway, SOX2	p53 − / − MEFs, HRASV12-expressing p53 − / − MEF, TIG-3, and TIG-3–SMR, HCT116, SW480, DLD1, HCC827, and H460	RAS/MAPK/CDK1 pathway induces enhanced O-GlcNAc modification and is required for expression of SOX2 and cancer stem cells generation	[14]
	miR-143-3p and miR-495-3p	HcerEpic, C4-1, HeLa, SiHa, and Caski	CDK1 was a target of miR-143-3p and miR-495-3p ↑↑ miR-143-3p or miR-495-3p: ↓ proliferation, migration, invasion, viability and ↑ apoptosis	[20]
	NCK1-AS1/miR-6857/CDK1 axis	CerEpiC, HeLa, C33A and SiHa and CaSki	∆ NCK1-AS1: ↓ proliferation and invasion, and ↑ cell cycle arrest NCK1-AS1 was found to sponge miR-6857, so regulate CDK1/6 protein translation	[21]
Cholangiocarcinoma	_	CCKS-1, TFK-1 and HUCCT-1	∆ CDK1: ↓ proliferation and invasion, and ↑ cell cycle arrest	[22]
Cholangiocarcinoma	PSMC2	HUCCT1, QBC939, RBE, and HCCC-9810	∆ PSMC2: ↓ proliferation, cell migration, ↑ cell cycle arrest, and apoptosis PSMC2 eas found to regulate its role via regulating CDK1	[23]
Colorectal cancer	KCTD12	HCT116 and HT29	Adefovir dipivoxil: ↓ proliferation, tumorigenesis, and ↑ G2 phase arrest via disrupting the CDK1-KCTD12 interaction ↑↑ CDK1: ↑ vemurafenib resistance	[16]
	MEK/ERK pathway	HT-29, RKO, VACO432, WiDr, DLD1, SW620, DiFi, A375, A19, T29 and VACO432, VT1, NB7	∆ CDK1: ↑ sensitivity to apoptosis A MEK/ERK inhibitor targeting CDK1 has effective role in reduction of cell proliferation	[15]
	miR-378a-5p	SW480, HCT116, SW620, HT-29 and NCM460	CDK1 was a target of miR-378a-5p ↑↑ miR-378a-5p: ↓ proliferation and migration ↑↑ CDK1: ↑ proliferation and migration	[24]
	DPP3	DLD-1, SW480, HCT 116, and RKO	∆ CDK1: ↓ inhibitory effects of DPP3 knockdown ∆ DPP3: ↓ proliferation, migration, ↑ apoptosis and cell cycle arrest DPP3 was found to regulate CRC via CDK1	[25]
	SNHG4/ miR-590-3p/CDK1 axis	FHC, HCT8, LoVo, HCT116, SW620, and HT29	∆ SNHG4: ↓ proliferation, viability, metastasis, and colony formation via targeting miR-590-3p and regulating CDK1	[26]
	NFE2L3, DUX4	HCT116 and HT29	∆ NFE2L3: ↑ levels of DUX4, which is an inhibitor of CDK1	[27]
	SNRPA1	SW480, RKO, HT-29, HCT116, and HEK293T	∆ SNRPA1: ↓ proliferation, ↑ apoptosis SNPRA1 was found to regulate CDK1 in CRC	[28]
Endometrial carcinoma	miR-1271	ECC-1, RL95-2, AN3 CA, and T-HESC	↑↑ miR-1271: ↓ cell proliferation, ↑ apoptosis via targeting CDK1	[29]
Esophageal squamous cell carcinoma	FAM135B, PI3K/Akt/mTOR signaling pathway	KYSE150, ECA109, TE-13, TE-10 and TE-1	∆ FAM135B: ↓ colony formation and ↓ cell cycle protein expression (pP53, CDK1), ↑ cell cycle arrest and ↑ radiosensitivity through regulating PI3K/Akt/mTOR	[30]
Gastric cancer	CASC11 and miR-340-5p	GES-1, MKN7, KATOIII and AZ521	∆ CASC11: ↓ proliferation, ↑ apoptosis and cell cycle arrest CASC11 regulated CDK1 via targeting miR-340-5p	[31]
	ESRRA, CDC25C-CDK1-Cyclin B1 pathway	HGC27, BGC823, MGC803, SGC7901 and GES-1	∆ ESRRA: ↓ cell viability, proliferation, migration, and invasion, EMT process, and ↑ apoptosis ESRRA/DSN1/CDC25C-CDK1-Cyclin B1 pathway was involved in in GC development	[32]
	CDCA5	MGC-803, SGC-7901, and BGC-823	∆ CDK1: ↓ proliferation, colon formation, migration, and invasion CDK1 and CDCA5 were co-expressed in GC cells	[33]
	ISL1	BGC823, MGC803, MKN28, and GES1	is CDK1 phosphorylated ISL1 at serine 269, thus promoted proliferation	[34]
Glioblastoma	p50, BCL-3, NF-κB	U87, A172, T98, U251, and GBM34	CDK1 was found to be up-regulated by temozolomide in an NF-κB related manner ∆ CDK1: ↑ sensitivity cells to temozolomide	[35]
Glioma	FOXD2-AS1/miR-31/CDK1 axis	SVG p12, T98, LN229, U87, U251, and 293FT	∆ FOXD2-AS1: ↓ proliferation, and ↑ cell cycle arrest FOXD2-AS1 was found to sponge miR-31, so regulated CDK1 levels	[36]
Hepatocellular carcinoma	PDK1/β-Catenin	MHCC97H (97H), LO2 and 97H liver cancer stem cells	∆ CDK1/PDK1/β-Catenin: ↓ EMT process RO3306 and sorafenib combination: ↓ 97H CSC growth	[37]
	DEPDC1B	HEP3B2.1-7, SK-HEP-1, huh-7, and HCCLM3	∆ DEPDC1B: ↓ proliferation, migration, colony formation, and ↑ G2 phase arrest, and cell apoptosis The function of DEPDC1B was found to be mediated by CDK1	[38]
	miR-1271-5p	SMMC-7721 and HuH-7	↑↑ miR-1271-5p: ↓ proliferation and ↑ radiosensitivity via targeting CDK1	[39]
	CDK1-PLK1/SGOL2/ANLN pathway	SK-Hep1	∆ CDK1: ↓ expression of PLK1, ANLN, and SGOL2 and resulted in a disordered cell cycle	[40]
	Upf1/SNORD52/CDK1 pathway	Huh7, HepG2, Hep3B, SK-Hep1, HCCLM9, HCCLM3, and HL-7702	∆ SNORD52: ↓ ↓ migration and invasion, and ↑ cell cycle arrest SNORD52 was found to regulate CDK1 by increasing the stability of CDK1 proteins	[41]
Leukemia	PLK1, Aurora B, and TRF1	HL-60	∆ CDK1: ↓ proliferation, ↑ cell cycle arrest via reducing the phosphorylation of PLK1 and Aurora B and negatively regulating TRF1	[42]
Lung cancer	Sox2	A549 and NCI-H520	∆ CDK1: ↑ chemotherapeutic sensitivity CDK1/Sox2 axis was found to regulate the stemness	[43]
	CASC11, miR-302	A547, H157, SPC-A-1 and 16HBE	∆ CASC11: ↓ proliferation via targeting miR-302 and regulating CDK1	[44]
	miR-34c-3p	A549, CALU-1, and HCC827	↑↑ miR-34c-3p: ↓ proliferation, ↑ apoptosis and in KRASmut cells via targeting CDK1	[45]
	NCK1-AS1	A549, NCI-H1299, PC-9 and NCI-H1650	∆ NCK1-AS1 (which regulated CDK1): ↓ proliferation	[46]
	miR-186	A549, H1299, H460, and BEAS-2	Lycorine treatment: ↑ levels of miR-186 and ↓ levels of CDK1: ↓ proliferation and ↑ apoptosis CDK1 was a target of miR-186	[47]
	GP130/STAT3 signaling pathway	A549, 1792, and HEK293T	↑↑ Iron-dependent CDK1 activity: ↑ activaty of the GP130/STAT3 signaling	[48]
	TMPO-AS1 and miR-143-3p	16HBE, H1299, A549, 95D, and H125	∆ TMPO-AS1: ↓ cell viability, ↑ apoptosis TMPO-AS1 regulated CDK1 via targeting miR-143-3p	[49]
	miR-181a	16HBE,, H1299, and A549	↑↑ miR-181a: ↓ proliferation, colony formation, and invasion	[50]
	miR-143 and miR-506	HFL-1, A549, H358, H69-AR, H358, H1975, and Calu-3	↑↑ miR-143 and miR-506: ↓ cell growth via targeting CDK1 and CDK4	[51]
	miR-143 and miR-506	A549, HUVECs	↑↑ miR-143 and miR-506: ↓ angiogenesis, and ↑ cell cycle arrest via targeting CDK1, 4/6 genes, respectively	[52]
Melanoma	Sox2	1205Lu, WM239A, A375, and HCT116	CDK1 was found to be a new regulator of Sox2, so had tumor-initiating capacity in melanoma	[53]
Melanoma	CHPF	A375	CHPF was found to play its oncogenic role by regulating of CDK1 in malignant melanoma	[54]
Myeloid leukemia	EZH2 and DNMT3A	NIH3T3, 293T, and OCI-AML3	↑↑ DNMT3A mutation-induced CDK1: ↑ proliferation and ↓ apoptosis via modulating the interaction between EZH2 and DNMT3A	[55]
Nasopharyngeal carcinoma	cyclin B1	5-8F and 6-10B NPC	Proteasome inhibitors were found to participate in the accretion of CDK1/cyclin B1, so decreased paclitaxel-induced cell death	[56]
	CDC25C/CDK1/Cyclin B1 pathway	CNE1 and CNE2	appropriate dose of tetrandrine and irradiation treatment: ↓ phosphorylation of CDK1 and CDC25C and ↑ expression of cyclin B1, ↑ cell cycle arrest	[57]
	miR-195-3p	5–8 F, 6–10B, CNE1, CNE2, C666-1, and NP69	↑↑ miR-195-3p: ↑ radiosensitivity via targeting CDK1	[58]
Ovarian cancer	UBE2C	KOV3, A2780, SKOV3/DDP, and A2780/ DDP	∆ UBE2C: ↓ proliferation, cisplatin resistance, and ↑ apoptosis via downregulating CDK1	[59]
	Chk1-CDC25C and P53-P21WAF1 signaling pathway	SK-OV-3 and OVCAR-3	∆ CDK1: ↓ proliferation, ↑ cell cycle arrest, and cell apoptosis	[60]
	TONSL-AS1 and miR-490-3p	OVCAR3 OEC cell line	↑↑ TONSL-AS1: ↑ proliferation via targeting miR-490-3p and regulating CDK1	[61]
	DLEU1/miR-490-3p/CDK1 axis	OVCAR3 and A2780	↑↑ DLEU1: ↑ proliferation, migration, and invasion, and ↓ apoptosis DLEU1 was found to sponge miR-490-3p, so regulate CDK1	[62]
Pancreatic cancer	KRas	MiaPaCa2, Panc1, L3.6pl, A549, A427, H460, Calu6, SW620, DLD1, HCT8	AT7519, (a CDK1, 2, 7, and 9 inhibitor) induces apoptosis CDK hyperactivation was linked with mt KRas dependency	[63]
Pancreatic cancer	miR-143 and miR-506	Panc-1 and MIA-PaCa-2	↑↑ miR-143 and miR-506: ↓ cell growth via targeting CDK1 and CDK4	[51]
Pancreatic ductal adenocarcinoma	_	PATU-T, Hs766T, and HPAF-II	Oxadiazole-based topsentin derivative (compound 6b): ↓ CDK1 expression, and ↑ apoptosis	[64]
Pancreatic ductal adenocarcinoma	_	different cell lines	Inaciclib was found to be an immune checkpoint inhibitor ∆ CDK1/2/5: ↓ UN-dependent STAT1 expression and activation, ↑ caspase-dependent apoptosis and histone-dependent ICD	[65]
Prostate cancer	TPX2, ERK/GSK3β/SNAIL signaling pathway	BPH-1, LNCaP, C4-2, PC-3, 22RV1	∆ TPX2: ↓ cell activity and migration, EMT process, ↓ expression of CDK1, ↓ the phosphorylation of ERK/GSK3β/SNAIL	[66]
Prostate cancer	ABCC5	C4-2, VCaP, ENZ-R, C4-2 and 22Rv1	↑↑ ABCC5: ↑ progression of cancer and resistance to Enzalutamide via the CDK1-mediated phosphorylation of AR ABCC5 was found to inhibit ubiquitination of CDK1 via binding to CDK1 ∆ CDK1: ↑ sensitivity to enzalutamide	[67]

∆ knock-down or deletion, ICD immunogenic cell death, EMT epithelial-mesenchymal transition, GC Gastric cancer, CRC Colorectal cancer

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