TY - JOUR
T1 - The tumor suppressor capability of p53 is dependent on nonmuscle myosin IIA function in head and neck cancer
AU - Coaxum, Sonya D.
AU - Tiedeken, Jessica
AU - Garrett-Mayer, Elizabeth
AU - Myers, Jeffrey
AU - Rosenzweig, Steven A.
AU - Neskey, David M.
N1 - Funding Information:
We wish to acknowledge the services of the Cell and Molecular Imaging Shared Resource-with a special thanks to Jennifer Bestman for immunofluorescence image acquisition and data analyses, Biostatistics Shared Resource and the Flow Cytometry and Cell Sorting Shared Resource, Hollings Cancer Center (supported by P30 CA 138313).This work was supported by the K12 Paul Calebresi Clinical and Translational Oncology Training Program K12 CA157688 (DMN), NIDCR K08 DE026542-01 (DMN), the American Cancer Society Institutional Research Grant IRG-97-291-14 (DMN), and NCI R01 CA 134845 (SAR).
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Head and neck squamous cell carcinoma
KW - Non-muscle myosin IIA
KW - TP53
KW - Tumor suppressor
UR - http://www.scopus.com/inward/record.url?scp=85016994059&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85016994059&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.14967
DO - 10.18632/oncotarget.14967
M3 - Article
C2 - 28160562
AN - SCOPUS:85016994059
SN - 1949-2553
VL - 8
SP - 22991
EP - 23007
JO - Oncotarget
JF - Oncotarget
IS - 14
ER -