Lung Cancer Stem Cells: Molecular Features and Therapeutic Targets

Overview

Journal Mol Aspects Med

Specialties Biochemistry
Molecular Biology

Date 2013 Sep 11

PMID 24016594

Citations 30

Authors

Sandeep Singh

Srikumar Chellappan

Affiliations

Soon will be listed here.

Abstract

Lung cancers are highly heterogeneous and resistant to available therapeutic agents, with a five year survival rate of less than 15%. Despite significant advances in our knowledge of the genetic alterations and aberrations in signaling pathways, it has been difficult to determine the basis of lung cancer heterogeneity and drug resistance. Cancer stem cell model has attracted a significant amount of attention in recent years as a viable explanation for the heterogeneity, drug resistance, dormancy and recurrence and metastasis of various tumors. At the same time, cancer stem cells have been relatively less characterized in lung cancers. This review summarizes the current understanding of lung cancer stem cells, including their molecular features and signaling pathways that drive their stemness. This review also discusses the potential startegies to inhibit the signaling pathways driving stemness, in an effort to eradicate these cells to combat lung cancer.

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References

Zemke A, Teisanu R, Giangreco A, Drake J, Brockway B, Reynolds S . beta-Catenin is not necessary for maintenance or repair of the bronchiolar epithelium. Am J Respir Cell Mol Biol. 2009; 41(5):535-43. PMC: 2778160. DOI: 10.1165/rcmb.2008-0407OC. View

Kirstetter P, Anderson K, Porse B, Jacobsen S, Nerlov C . Activation of the canonical Wnt pathway leads to loss of hematopoietic stem cell repopulation and multilineage differentiation block. Nat Immunol. 2006; 7(10):1048-56. DOI: 10.1038/ni1381. View

Chen J, Li Y, Yu T, McKay R, Burns D, Kernie S . A restricted cell population propagates glioblastoma growth after chemotherapy. Nature. 2012; 488(7412):522-6. PMC: 3427400. DOI: 10.1038/nature11287. View

Uematsu K, He B, You L, Xu Z, McCormick F, Jablons D . Activation of the Wnt pathway in non small cell lung cancer: evidence of dishevelled overexpression. Oncogene. 2003; 22(46):7218-21. DOI: 10.1038/sj.onc.1206817. View

Jiang F, Qiu Q, Khanna A, Todd N, Deepak J, Xing L . Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer. Mol Cancer Res. 2009; 7(3):330-8. PMC: 4255559. DOI: 10.1158/1541-7786.MCR-08-0393. View

Halpern M, Warner K . Motivations for smoking cessation: a comparison of successful quitters and failures. J Subst Abuse. 1993; 5(3):247-56. DOI: 10.1016/0899-3289(93)90066-k. View

Shi M, Xiong Y, Jia X, Li X, Zhang L, Li X . Fluorouracil selectively enriches stem-like cells in the lung adenocarcinoma cell line SPC. Tumour Biol. 2013; 34(3):1503-10. DOI: 10.1007/s13277-013-0675-5. View

Tsao P, Chen F, Izvolsky K, Walker J, Kukuruzinska M, Lu J . Gamma-secretase activation of notch signaling regulates the balance of proximal and distal fates in progenitor cells of the developing lung. J Biol Chem. 2008; 283(43):29532-44. PMC: 2570893. DOI: 10.1074/jbc.M801565200. View

Reynolds S, Zemke A, Giangreco A, Brockway B, Teisanu R, Drake J . Conditional stabilization of beta-catenin expands the pool of lung stem cells. Stem Cells. 2008; 26(5):1337-46. PMC: 2773682. DOI: 10.1634/stemcells.2008-0053. View

10.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

11.

Chute J, Muramoto G, Whitesides J, Colvin M, Safi R, Chao N . Inhibition of aldehyde dehydrogenase and retinoid signaling induces the expansion of human hematopoietic stem cells. Proc Natl Acad Sci U S A. 2006; 103(31):11707-12. PMC: 1544234. DOI: 10.1073/pnas.0603806103. View

12.

Cortes-Dericks L, Galetta D, Spaggiari L, Schmid R, Karoubi G . High expression of octamer-binding transcription factor 4A, prominin-1 and aldehyde dehydrogenase strongly indicates involvement in the initiation of lung adenocarcinoma resulting in shorter disease-free intervals. Eur J Cardiothorac Surg. 2012; 41(6):e173-81. DOI: 10.1093/ejcts/ezs170. View

13.

Bender Kim C, Jackson E, Woolfenden A, Lawrence S, Babar I, Vogel S . Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell. 2005; 121(6):823-35. DOI: 10.1016/j.cell.2005.03.032. View

14.

Taipale J, Beachy P . The Hedgehog and Wnt signalling pathways in cancer. Nature. 2001; 411(6835):349-54. DOI: 10.1038/35077219. View

15.

Borthwick D, Shahbazian M, Krantz Q, Dorin J, Randell S . Evidence for stem-cell niches in the tracheal epithelium. Am J Respir Cell Mol Biol. 2001; 24(6):662-70. DOI: 10.1165/ajrcmb.24.6.4217. View

16.

Zhou S, Schuetz J, Bunting K, Colapietro A, Sampath J, Morris J . The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med. 2001; 7(9):1028-34. DOI: 10.1038/nm0901-1028. View

17.

Shien K, Toyooka S, Yamamoto H, Soh J, Jida M, Thu K . Acquired resistance to EGFR inhibitors is associated with a manifestation of stem cell-like properties in cancer cells. Cancer Res. 2013; 73(10):3051-61. PMC: 4506773. DOI: 10.1158/0008-5472.CAN-12-4136. View

18.

Curtis S, Sinkevicius K, Li D, Lau A, Roach R, Zamponi R . Primary tumor genotype is an important determinant in identification of lung cancer propagating cells. Cell Stem Cell. 2010; 7(1):127-33. PMC: 2908996. DOI: 10.1016/j.stem.2010.05.021. View

19.

Mizugaki H, Sakakibara-Konishi J, Kikuchi J, Moriya J, Hatanaka K, Kikuchi E . CD133 expression: a potential prognostic marker for non-small cell lung cancers. Int J Clin Oncol. 2013; 19(2):254-9. DOI: 10.1007/s10147-013-0541-x. View

20.

Xu C, Xie D, Yu S, Yang X, He L, Yang J . β-Catenin/POU5F1/SOX2 transcription factor complex mediates IGF-I receptor signaling and predicts poor prognosis in lung adenocarcinoma. Cancer Res. 2013; 73(10):3181-9. DOI: 10.1158/0008-5472.CAN-12-4403. View