Identification of Sca-1+Abcg1+ bronchioalveolar epithelial cells as the origin of lung adenocarcinoma in Gprc5a-knockout mouse model through the interaction between lung progenitor AT2 and Lgr5 cells.

Oncogene
Huijing YinWei Jin

Abstract

The reason for the reduced efficacy of lung cancer therapy is the existence of lung cancer stem cells (CSCs). Targeting CSCs results in evolved phenotypes with increased malignancy, leading to therapy failure. Here, we propose a new therapeutic strategy: investigating the "transitional" cells that represent the stage between normal lung stem cells and lung CSCs. Identifying and targeting the key molecule that drives carcinogenesis to inhibit or reverse this process would thus provide new perspectives for early diagnosis and intervention in lung cancer. We used Gprc5a-knockout (KO) mice, the first animal model of spontaneous lung adenocarcinoma established by the deletion of a single lung tumor suppressor gene. We investigated the interaction of lung progenitor cells AT2 with Lgr5 cells in the generation of CSCs and related signaling mechanism. In the present study, using Gprc5a-KO mice, we found the initiator Sca-1+Abcg1+ subset with a CSC-like phenotype within the lung progenitor AT2 cell population in mice that had not yet developed tumors. We confirmed the self-renewal and tumor initiation capacities of this subset in vitro, in vivo, and clinical samples. Mechanistically, we found that the generation of Sca-1+Abcg1+ cells wa...Continue Reading

References

Nov 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·A BhattacharjeeM Meyerson
Nov 12, 2002·The Journal of Biological Chemistry·Roy R HantganJohn W Weisel
Oct 2, 2004·Nature Reviews. Molecular Cell Biology·Wenjun Guo, Filippo G Giancotti
Jul 20, 2006·Proceedings of the National Academy of Sciences of the United States of America·Paul P SzotekPatricia K Donahoe
Jul 28, 2007·The Journal of Clinical Investigation·Xun WangDaniel J Rader
Nov 15, 2007·Journal of the National Cancer Institute·Qingguo TaoReuben Lotan
May 10, 2008·Briefings in Functional Genomics & Proteomics·Xiaofeng Ye, Reuben Lotan
Oct 14, 2008·Nature Genetics·Viljar JaksRune Toftgård
Dec 8, 2009·Science·Richard O Hynes
Jun 10, 2010·The Journal of Clinical Investigation·Jeffrey M SturekCatherine C Hedrick
Mar 18, 2011·Genome Biology·Adam RobertsLior Pachter
Jun 28, 2011·The Journal of Clinical Investigation·Harold A ChapmanThiennu H Vu
Feb 22, 2012·The Journal of Cell Biology·Pengfei LuZena Werb
Mar 6, 2012·Nature Methods·Ben Langmead, Steven L Salzberg
Nov 17, 2012·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Junya FujimotoIgnacio I Wistuba
Nov 20, 2012·Nature Methods·Adam Roberts, Lior Pachter
Jan 15, 2013·Targeted Oncology·Brian J MorrisonJason C Steel
Jan 21, 2014·Current Topics in Developmental Biology·Kristen T LeemanCarla F Kim
Apr 4, 2014·Bioinformatics·Anthony M BolgerBjoern Usadel
Dec 3, 2014·Cellular Signalling·Kyung-Min LeeIncheol Shin
Mar 7, 2015·Cancer Research·Shuangshuang ZhongJiong Deng
Mar 10, 2015·Nature Methods·Daehwan KimSteven L Salzberg
Apr 8, 2016·American Journal of Physiology. Cell Physiology·Anette M Høye, Janine T Erler
May 10, 2017·Cell·Nina Cabezas-WallscheidAndreas Trumpp

❮ Previous
Next ❯

Citations

Aug 11, 2020·IScience·Zhichao LiWeiren Huang

❮ Previous
Next ❯

Methods Mentioned

BETA
acetylation
flow cytometry
immunoprecipitation
xenograft
PCR
transfection
co-IP
RNA-seq
proximity ligation assay
Flow

Software Mentioned

DESeq
ImageJ
hisat2
WinMDI
NIS Viewer
eXpress
bowtie2

Related Concepts

Related Papers

Current Cancer Drug Targets
Samriddhi ShuklaSyed Musthapa Meeran
Cancer Treatment Reviews
Xiaodan WuXiangdong Wang
Cell Death Discovery
Ayobami Matthew OlajuyinHong-Long Ji
Zhongguo fei ai za zhi = Chinese journal of lung cancer
Huijing Yin, Jiong Deng
© 2021 Meta ULC. All rights reserved