Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10050)
Regulator Name Kinesin-like protein KIF20A (KIF20A)
Synonyms
MKLP2, RAB6KIFL; GG10_2; Mitotic kinesin-like protein 2; Rab6-interacting kinesin-like protein; Rabkinesin-6
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Gene Name KIF20A
Gene ID 10112
Regulator Type Protein coding
Uniprot ID O95235
Sequence
MSQGILSPPAGLLSDDDVVVSPMFESTAADLGSVVRKNLLSDCSVVSTSLEDKQQVPSED
SMEKVKVYLRVRPLLPSELERQEDQGCVRIENVETLVLQAPKDSFALKSNERGIGQATHR
FTFSQIFGPEVGQASFFNLTVKEMVKDVLKGQNWLIYTYGVTNSGKTHTIQGTIKDGGIL
PRSLALIFNSLQGQLHPTPDLKPLLSNEVIWLDSKQIRQEEMKKLSLLNGGLQEEELSTS
LKRSVYIESRIGTSTSFDSGIAGLSSISQCTSSSQLDETSHRWAQPDTAPLPVPANIRFS
IWISFFEIYNELLYDLLEPPSQQRKRQTLRLCEDQNGNPYVKDLNWIHVQDAEEAWKLLK
VGRKNQSFASTHLNQNSSRSHSIFSIRILHLQGEGDIVPKISELSLCDLAGSERCKDQKS
GERLKEAGNINTSLHTLGRCIAALRQNQQNRSKQNLVPFRDSKLTRVFQGFFTGRGRSCM
IVNVNPCASTYDETLHVAKFSAIASQLVHAPPMQLGFPSLHSFIKEHSLQVSPSLEKGAK
ADTGLDDDIENEADISMYGKEELLQVVEAMKTLLLKERQEKLQLEMHLRDEICNEMVEQM
QQREQWCSEHLDTQKELLEEMYEEKLNILKESLTSFYQEEIQERDEKIEELEALLQEARQ
QSVAHQQSGSELALRRSQRLAASASTQQLQEVKAKLQQCKAELNSTTEELHKYQKMLEPP
PSAKPFTIDVDKKLEEGQKNIRLLRTELQKLGESLQSAERACCHSTGAGKLRQALTTCDD
ILIKQDQTLAELQNNMVLVKLDLRKKAACIAEQYHTVLKLQGQVSAKKRLGTNQENQQPN
QQPPGKKPFLRNLLPRTPTCQSSTDCSPYARILRSRRSPLLKSGPFGKKY

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Family TRAFAC class myosin-kinesin ATPase superfamily, Kinesin family
Function
Mitotic kinesin required for chromosome passenger complex (CPC)-mediated cytokinesis. Following phosphorylation by PLK1, involved in recruitment of PLK1 to the central spindle. Interacts with guanosine triphosphate (GTP)-bound forms of RAB6A and RAB6B. May act as a motor required for the retrograde RAB6 regulated transport of Golgi membranes and associated vesicles along microtubules. Has a microtubule plus end- directed motility.

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HGNC ID
HGNC:9787
KEGG ID hsa:10112
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
KIF20A can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
Nuclear factor erythroid 2-related factor 2 (NFE2L2) [Suppressor; Marker]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
NCI-H716 cells Cecum adenocarcinoma Homo sapiens CVCL_1581
In Vivo Model
HCT116-Or or H716 cells (7*106) were suspended into 200 ul matrigel (BD Bioscience), and injected into the subcutaneous tissues of mouse right lower limbs. Animals were grouped randomly (eight mouse per group) and medication was initiated when the average xenograft size was over 100 mm3: Oxaliplatin was given alone weekly through intraperitoneal injection (5 mg/kg), or in combination with liproxstatin-1 through intraperitoneal injection for twice a week (125 mg/kg) and RSL3 through intra-tumor injection (100 mg/kg, in order to achieve better local concentration and reduce the probable systemic toxicity of RSL3) weekly.

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Response regulation KIF20A was highly expressed in the oxaliplatin-resistant cell lines and was strongly correlated with survival among colorectal cancer patients. Silencing KIF20A enhanced cellular sensitivity to oxaliplatin both in vivo and in vitro, and silencing KIF20A also suppressed NUAK1 activation. Moreover, silencing NUAK1 up-regulated the expression of PP1, down-regulated the phosphorylation of downstream GSK3Ser9, suppressed the nuclear import of Nrf2, inhibited the expression of a ferroptosis key negative regulatory protein (GPX4), and blocked cellular resistance.
Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [2]
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
 HEK-293T cells Normal Homo sapiens CVCL_0063
16HBE14o- cells Normal Homo sapiens CVCL_0112
NCI-H358 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
PC-9 cells Lung adenocarcinoma Homo sapiens CVCL_B260
HCC827 cells Lung adenocarcinoma Homo sapiens CVCL_2063
NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
Response regulation GEM and the ferroptosis inducer IKE synergistically inhibited the proliferation of lung adenocarcinoma (LUAD) cells. Targeting the FRG KIF20A can enhance ferroptosis and modulate the combination of GEM and IKE, which might serve as a therapeutic target in LUAD.
Colorectal cancer [ICD-11: 2B91]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Kinesin-like protein KIF20A (KIF20A) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
NCI-H716 cells Cecum adenocarcinoma Homo sapiens CVCL_1581
In Vivo Model
HCT116-Or or H716 cells (7*106) were suspended into 200 ul matrigel (BD Bioscience), and injected into the subcutaneous tissues of mouse right lower limbs. Animals were grouped randomly (eight mouse per group) and medication was initiated when the average xenograft size was over 100 mm3: Oxaliplatin was given alone weekly through intraperitoneal injection (5 mg/kg), or in combination with liproxstatin-1 through intraperitoneal injection for twice a week (125 mg/kg) and RSL3 through intra-tumor injection (100 mg/kg, in order to achieve better local concentration and reduce the probable systemic toxicity of RSL3) weekly.

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Response regulation KIF20A was highly expressed in the oxaliplatin-resistant cell lines and was strongly correlated with survival among colorectal cancer patients. Silencing KIF20A enhanced cellular sensitivity to oxaliplatin both in vivo and in vitro, and silencing KIF20A also suppressed NUAK1 activation. Moreover, silencing NUAK1 up-regulated the expression of PP1, down-regulated the phosphorylation of downstream GSK3Ser9, suppressed the nuclear import of Nrf2, inhibited the expression of a ferroptosis key negative regulatory protein (GPX4), and blocked cellular resistance.
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Kinesin-like protein KIF20A (KIF20A) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
 HEK-293T cells Normal Homo sapiens CVCL_0063
16HBE14o- cells Normal Homo sapiens CVCL_0112
NCI-H358 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
PC-9 cells Lung adenocarcinoma Homo sapiens CVCL_B260
HCC827 cells Lung adenocarcinoma Homo sapiens CVCL_2063
NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
Response regulation GEM and the ferroptosis inducer IKE synergistically inhibited the proliferation of lung adenocarcinoma (LUAD) cells. Targeting the FRG KIF20A can enhance ferroptosis and modulate the combination of GEM and IKE, which might serve as a therapeutic target in LUAD.
References
Ref 1 Suppressing the KIF20A/NUAK1/Nrf2/GPX4 signaling pathway induces ferroptosis and enhances the sensitivity of colorectal cancer to oxaliplatin. Aging (Albany NY). 2021 Mar 26;13(10):13515-13534. doi: 10.18632/aging.202774. Epub 2021 Mar 26.
Ref 2 KIF20A is associated with clinical prognosis and synergistic effect of gemcitabine combined with ferroptosis inducer in lung adenocarcinoma. Front Pharmacol. 2022 Sep 26;13:1007429. doi: 10.3389/fphar.2022.1007429. eCollection 2022.