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Hedgehog pathway maintains cell survival under stress conditions, and drives drug resistance in lung adenocarcinoma.

Hedgehog (HH) pathway plays an important role in embryonic development, but is largely inactive in adult except for tissue repair. Aberrant activation of HH pathway has been found in a variety of cancer types. In non-small cell lung cancer, however, the role and importance of HH pathway remain contr... Full description

Journal Title: Oncotarget April 26, 2016, Vol.7(17), pp.24179-24193
Main Author: Lin, Erh-Hsuan
Other Authors: Kao, Yu-Rung , Lin, Chih-An , Kuo, Ting-Yu , Yang, Sheng-Ping , Hsu, Chiung-Fang , Chou, Teh-Ying , Ho, Chao-Chi , Wu, Cheng-Wen
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1949-2553 ; DOI: 10.18632/oncotarget.8253
Link: http://search.proquest.com/docview/1808374748/?pq-origsite=primo
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title: Hedgehog pathway maintains cell survival under stress conditions, and drives drug resistance in lung adenocarcinoma.
format: Article
creator:
  • Lin, Erh-Hsuan
  • Kao, Yu-Rung
  • Lin, Chih-An
  • Kuo, Ting-Yu
  • Yang, Sheng-Ping
  • Hsu, Chiung-Fang
  • Chou, Teh-Ying
  • Ho, Chao-Chi
  • Wu, Cheng-Wen
subjects:
  • Adenocarcinoma–Drug Therapy
  • Animals–Metabolism
  • Apoptosis–Pathology
  • Biomarkers, Tumor–Drug Effects
  • Carcinoma, Non-Small-Cell Lung–Metabolism
  • Carrier Proteins–Drug Therapy
  • Cell Proliferation–Metabolism
  • Drug Resistance, Neoplasm–Pathology
  • Hedgehog Proteins–Metabolism
  • Humans–Drug Effects
  • Lung Neoplasms–Metabolism
  • Membrane Glycoproteins–Drug Therapy
  • Mice–Metabolism
  • Mice, Inbred Balb C–Pathology
  • Mice, Nude–Metabolism
  • Protein Kinase Inhibitors–Pharmacology
  • Signal Transduction–Drug Effects
  • Stress, Physiological–Drug Effects
  • Tumor Cells, Cultured–Drug Effects
  • Xenograft Model Antitumor Assays–Drug Effects
  • Biomarkers, Tumor
  • Carrier Proteins
  • Hhip Protein, Human
  • Hedgehog Proteins
  • Membrane Glycoproteins
  • Protein Kinase Inhibitors
  • Hgf/Met
  • Hhip
  • Hedgehog Pathway
  • Drug Resistance
  • Lung Adenocarcinoma
ispartof: Oncotarget, April 26, 2016, Vol.7(17), pp.24179-24193
description: Hedgehog (HH) pathway plays an important role in embryonic development, but is largely inactive in adult except for tissue repair. Aberrant activation of HH pathway has been found in a variety of cancer types. In non-small cell lung cancer, however, the role and importance of HH pathway remain controversial. In the current study, we found that HH pathway was maintained in low activity in lung adenocarcinoma (LAC) cells under normal culture condition, but was highly induced in response to stress conditions. Activation of HH pathway promoted cell survival, growth, and invasion partially through HGF and MET signaling. Hedgehog-Interacting Protein (HHIP), a cell-surface negative regulator of HH pathway, was epigenetically silenced in LAC. Overexpression of HHIP blocked the activation of HH and HGF/MET pathways, and made cells significantly more susceptible to stress conditions. In LAC cells with acquired resistance to Epidermal Growth Factor Receptor Tyrosin Kinase Inhibitor (EGFR-TKI), we...
language: eng
source:
identifier: E-ISSN: 1949-2553 ; DOI: 10.18632/oncotarget.8253
fulltext: fulltext
issn:
  • 19492553
  • 1949-2553
url: Link


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titleHedgehog pathway maintains cell survival under stress conditions, and drives drug resistance in lung adenocarcinoma.
creatorLin, Erh-Hsuan ; Kao, Yu-Rung ; Lin, Chih-An ; Kuo, Ting-Yu ; Yang, Sheng-Ping ; Hsu, Chiung-Fang ; Chou, Teh-Ying ; Ho, Chao-Chi ; Wu, Cheng-Wen
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ispartofOncotarget, April 26, 2016, Vol.7(17), pp.24179-24193
identifierE-ISSN: 1949-2553 ; DOI: 10.18632/oncotarget.8253
subjectAdenocarcinoma–Drug Therapy ; Animals–Metabolism ; Apoptosis–Pathology ; Biomarkers, Tumor–Drug Effects ; Carcinoma, Non-Small-Cell Lung–Metabolism ; Carrier Proteins–Drug Therapy ; Cell Proliferation–Metabolism ; Drug Resistance, Neoplasm–Pathology ; Hedgehog Proteins–Metabolism ; Humans–Drug Effects ; Lung Neoplasms–Metabolism ; Membrane Glycoproteins–Drug Therapy ; Mice–Metabolism ; Mice, Inbred Balb C–Pathology ; Mice, Nude–Metabolism ; Protein Kinase Inhibitors–Pharmacology ; Signal Transduction–Drug Effects ; Stress, Physiological–Drug Effects ; Tumor Cells, Cultured–Drug Effects ; Xenograft Model Antitumor Assays–Drug Effects ; Biomarkers, Tumor ; Carrier Proteins ; Hhip Protein, Human ; Hedgehog Proteins ; Membrane Glycoproteins ; Protein Kinase Inhibitors ; Hgf/Met ; Hhip ; Hedgehog Pathway ; Drug Resistance ; Lung Adenocarcinoma
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descriptionHedgehog (HH) pathway plays an important role in embryonic development, but is largely inactive in adult except for tissue repair. Aberrant activation of HH pathway has been found in a variety of cancer types. In non-small cell lung cancer, however, the role and importance of HH pathway remain controversial. In the current study, we found that HH pathway was maintained in low activity in lung adenocarcinoma (LAC) cells under normal culture condition, but was highly induced in response to stress conditions. Activation of HH pathway promoted cell survival, growth, and invasion partially through HGF and MET signaling. Hedgehog-Interacting Protein (HHIP), a cell-surface negative regulator of HH pathway, was epigenetically silenced in LAC. Overexpression of HHIP blocked the activation of HH and HGF/MET pathways, and made cells significantly more susceptible to stress conditions. In LAC cells with acquired resistance to Epidermal Growth Factor Receptor Tyrosin Kinase Inhibitor (EGFR-TKI), we...
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titleHedgehog pathway maintains cell survival under stress conditions, and drives drug resistance in lung adenocarcinoma.
authorLin, Erh-Hsuan ; Kao, Yu-Rung ; Lin, Chih-An ; Kuo, Ting-Yu ; Yang, Sheng-Ping ; Hsu, Chiung-Fang ; Chou, Teh-Ying ; Ho, Chao-Chi ; Wu, Cheng-Wen
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