The tumor suppressor capability of p53 is dependent on non-muscle myosin IIA function in head and neck cancer.
Over 300,000 patients develop squamous cell carcinoma of the head and neck (HNSCC) worldwide with 25-30% of patients ultimately dying from their disease. Currently, molecular biomarkers are not used in HNSCC but several genes have been identified including mutant TP53 (mutp53). Our recent work has identified an approach to stratify patients with tumors harboring high or low risk TP53 mutations. Non-muscle Myosin IIA (NMIIA) was recently identified as a tumor suppressor in HNSCC. We now demonstrate that low MYH9 expression is associated with decreased survival in patients with head and neck cancer harboring low-risk mutp53 but not high-risk mutp53. Furthermore, inhibition of NMIIA leads to increased invasion in cells harboring wildtype p53 (wtp53), which was not observed in high-risk mutp53 cells. This increased invasiveness of wtp53 following NMIIA inhibition was associated with reduced p53 target gene expression and was absent in cells expressing mutp53. This reduced expression may be due, in part, to a decrease in nuclear localization of wtp53. These findings suggest that the tumor suppressor capability of wtp53 is dependent upon functional NMIIA and that the invasive phenotype of high-risk mutp53 is independent of NMIIA.
Department of Otolaryngology, Head and Neck Surgery, Medical University of South Carolina, Charleston, SC, USA.
Sonya D
SD
Coaxum
Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, USA.
Jessica
J
Tiedeken
Department of Public Health Sciences and Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
Elizabeth
E
Garrett-Mayer
Department of Head & Neck Surgery, M.D. Anderson Medical Center, Houston, TX, USA.
Jeffrey
J
Myers
Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, USA.
Steven A
SA
Rosenzweig
Department of Otolaryngology, Head and Neck Surgery, Medical University of South Carolina, Charleston, SC, USA.|Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, USA.
David M
DM
Neskey
D017209:Apoptosis / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020409:Molecular Motor Proteins / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D018995:Myosin Heavy Chains
TP53; head and neck squamous cell carcinoma; non-muscle myosin IIA; tumor suppressor