RGD Reference Report - Mutant p53 promotes cell spreading and migration via ARHGAP44. - Rat Genome Database

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Mutant p53 promotes cell spreading and migration via ARHGAP44.

Authors: Xu, Jinjin  Jiao, Jian  Xu, Wei  Ji, Lei  Jiang, Dongjie  Xie, Shaofang  Kubra, Syeda  Li, Xiaotao  Fu, Junjiang  Xiao, Jianru  Zhang, Bianhong 
Citation: Xu J, etal., Sci China Life Sci. 2017 Sep;60(9):1019-1029. doi: 10.1007/s11427-016-9040-8. Epub 2017 May 16.
RGD ID: 401901290
Pubmed: PMID:28527113   (View Abstract at PubMed)
DOI: DOI:10.1007/s11427-016-9040-8   (Journal Full-text)

The tumor suppressor p53 protein is either lost or mutated in about half of all human cancers. Loss of p53 function is well known to influence cell spreading, migration and invasion. While expression of mutant p53 is not equivalent to p53 loss, mutant p53 can acquire new functions to drive cell spreading and migration via different mechanisms. In our study, we found that mutant p53 significantly increased cell spreading and migration when comparing with p53-null cells. RNA-Seq analysis suggested that Rho GTPase activating protein 44 (ARHGAP44) is a new target of mutant p53, which suppressed ARHGAP44 transcription. ARHGAP44 has GAP activity and catalyze GTP hydrolysis on Cdc42. Higher level of GTP-Cdc42 was correlated with increase expression of mutant p53 and reduced ARHGAP44. Importantly, wt-ARHGAP44 but not mutant ARHGAP44 (R291A) suppressed mutant p53 mediated cell spreading and migration. Bioinformatics analysis indicated lower expression of ARHGAP44 in lung carcinoma compared with normal tissues, which was verified by RT-qPCR using specimens from patients. More interestingly, ARHGAP44 mRNA level was lower in tumors with mutant p53 than those with normal p53. Collectively, our results disclose a new mechanism by which mutant p53 stimulates cell spreading and migration.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
lung adenocarcinoma  HEP 401901290mRNA:decreased expression:lung (human)RGD 
lung adenocarcinoma  ISOARHGAP44 (Homo sapiens)401901290; 401901290mRNA:decreased expression:lung (human)RGD 
lung carcinoma  IEP 401901290mRNA:decreased expression:lung (human)RGD 
lung carcinoma  ISOARHGAP44 (Homo sapiens)401901290; 401901290mRNA:decreased expression:lung (human)RGD 
lung large cell carcinoma  HEP 401901290mRNA:decreased expression:lung (human)RGD 
lung large cell carcinoma  ISOARHGAP44 (Homo sapiens)401901290; 401901290mRNA:decreased expression:lung (human)RGD 
lung squamous cell carcinoma  HEP 401901290mRNA:decreased expression:lung (human)RGD 
lung squamous cell carcinoma  ISOARHGAP44 (Homo sapiens)401901290; 401901290mRNA:decreased expression:lung (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Arhgap44  (Rho GTPase activating protein 44)

Genes (Mus musculus)
Arhgap44  (Rho GTPase activating protein 44)

Genes (Homo sapiens)
ARHGAP44  (Rho GTPase activating protein 44)


Additional Information