INPP4B-mediated tumor resistance is associated with modulation of glucose metabolism via hexokinase 2 regulation in laryngeal cancer cells.
Inositol polyphosphate 4-phosphatase type II (INPP4B) was recently identified as a tumor resistance factor in laryngeal cancer cells. Herein, we show that INPP4B-mediated resistance is associated with increased glycolytic phenotype. INPP4B expression was induced by hypoxia and irradiation. Intriguingly, overexpression of INPP4B enhanced aerobic glycolysis. Of the glycolysis-regulatory genes, hexokinase 2 (HK2) was mainly regulated by INPP4B and this regulation was mediated through the Akt-mTOR pathway. Notably, codepletion of INPP4B and HK2 markedly sensitized radioresistant laryngeal cancer cells to irradiation or anticancer drug. Moreover, INPP4B was significantly associated with HK2 in human laryngeal cancer tissues. Therefore, these results suggest that INPP4B modulates aerobic glycolysis via HK2 regulation in radioresistant laryngeal cancer cells.
Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
Joong Won
JW
Min
Kwang Il
KI
Kim
Hyun-Ah
HA
Kim
Eun-Kyu
EK
Kim
Woo Chul
WC
Noh
Hong Bae
HB
Jeon
Dong-Hyung
DH
Cho
Jeong Su
JS
Oh
In-Chul
IC
Park
Sang-Gu
SG
Hwang
Jae-Sung
JS
Kim
D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007822:Laryngeal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D007830:Larynx / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
D000970:Antineoplastic Agents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D006593:Hexokinase; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D010744:Phosphoric Monoester Hydrolases; C053153:phosphatidylinositol-3,4-bisphosphate 4-phosphatase; D005947:Glucose
ERK-1/2; FDG; Glycolysis; HIF-1α; HK2; INPP4B; Laryngeal cancer; PI3K; PTEN; RR-HEp-2; Tumor resistance; extracellular signal-regulated protein kinase-1/2; fluorodeoxyglucose; hexokinase 2; hypoxia-inducible factor-1α; inositol polyphosphate 4-phosphatase Type II; phosphatase and tensin homolog; phosphoinositide 3-kinases; radioresistant HEp-2; siRNA; small interfering RNA