TY - JOUR
T1 - ADH1B promotes mesothelial clearance and ovarian cancer infiltration
AU - Gharpure, Kshipra M.
AU - Lara, Olivia D.
AU - Wen, Yunfei
AU - Pradeep, Sunila
AU - LaFargue, Chris
AU - Ivan, Cristina
AU - Rupaimoole, Rajesha
AU - Hu, Wei
AU - Mangala, Lingegowda S.
AU - Wu, Sherry Y.
AU - Nagaraja, Archana S.
AU - Baggerly, Keith
AU - Sood, Anil K.
N1 - Publisher Copyright:
© Gharpure et al.
PY - 2018/5/18
Y1 - 2018/5/18
N2 - Primary debulking surgery followed by adjuvant chemotherapy is the standard treatment for ovarian cancer. Residual disease after primary surgery is associated with poor patient outcome. Previously, we discovered ADH1B to be a molecular biomarker of residual disease. In the current study, we investigated the functional role of ADH1B in promoting ovarian cancer cell invasiveness and contributing to residual disease. We discovered that ADH1B overexpression leads to a more infiltrative cancer cell phenotype, promotes metastasis, increases the adhesion of cancer cells to mesothelial cells, and increases extracellular matrix degradation. Live cell imaging revealed that ADH1B-overexpressing cancer cells efficiently cleared the mesothelial cell layer compared to control cells. Moreover, gene array analysis revealed that ADH1B affects several pathways related to the migration and invasion of cancer cells. We also discovered that hypoxia increases ADH1B expression in ovarian cancer cells. Collectively, these findings indicate that ADH1B plays an important role in the pathways that promote ovarian cancer cell infiltration and may increase the likelihood of residual disease following surgery.
AB - Primary debulking surgery followed by adjuvant chemotherapy is the standard treatment for ovarian cancer. Residual disease after primary surgery is associated with poor patient outcome. Previously, we discovered ADH1B to be a molecular biomarker of residual disease. In the current study, we investigated the functional role of ADH1B in promoting ovarian cancer cell invasiveness and contributing to residual disease. We discovered that ADH1B overexpression leads to a more infiltrative cancer cell phenotype, promotes metastasis, increases the adhesion of cancer cells to mesothelial cells, and increases extracellular matrix degradation. Live cell imaging revealed that ADH1B-overexpressing cancer cells efficiently cleared the mesothelial cell layer compared to control cells. Moreover, gene array analysis revealed that ADH1B affects several pathways related to the migration and invasion of cancer cells. We also discovered that hypoxia increases ADH1B expression in ovarian cancer cells. Collectively, these findings indicate that ADH1B plays an important role in the pathways that promote ovarian cancer cell infiltration and may increase the likelihood of residual disease following surgery.
KW - Alcohol dehydrogenase
KW - ECM degradation
KW - Mesothelial clearance
KW - Residual disease
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U2 - 10.18632/oncotarget.25344
DO - 10.18632/oncotarget.25344
M3 - Article
C2 - 29861857
AN - SCOPUS:85047209178
SN - 1949-2553
VL - 9
SP - 25115
EP - 25126
JO - Oncotarget
JF - Oncotarget
IS - 38
ER -