Wnt/β-catenin signaling regulates cancer stem cells in lung cancer A549 cells

Teng, Ying; Wang, Xiuwen; Wang, Yawei; Ma, Daoxin

doi:10.1016/j.bbrc.2010.01.028

Cited by 216 publications

(172 citation statements)

References 28 publications

Supporting

Mentioning

160

Contrasting

Unclassified

Order By: Relevance

“…Wnt/β-catenin signaling controls proliferation, clone formation, migration and drug resistance abilities as well as the expression of cyclin D1 and OCT-4 in A549-derived lung cancer stem cells (40). In addition, survivin expression is downregulated by β-catenin/TCF-4 signaling inhibition with APC, another Wnt inhibitor, which increases apoptosis of cancer stem cells and other proliferative cells in the lower crypt, thereby preventing the expansion of cancer stem cells and initiation of colon carcinogenesis (41).…”

Section: Discussionmentioning

confidence: 99%

Dickkopf-3 (Dkk3) induces apoptosis in cisplatin-resistant lung adenocarcinoma cells via the Wnt/β-catenin pathway

Wang

et al. 2014

Oncology Reports

View full text Add to dashboard Cite

Abstract. Previous studies have shown that is inactivated in lung cancer cells, while the inactivation of the Wnt/β-catenin signaling pathway by Dkk3 inhibits lung cancer progression. In the present study, we investigated whether Dkk3 enhances the sensitivity of lung cancer cells to cisplatin. A549, Calu1 and H460 lung adenocarcinoma cell lines were transfected with DKK3 siRNA, while the cisplatin-resistant subline A549cis was transfected with DKK3. DKK3 expression was attenuated in A549cis, Calu1cis and H460cis compared to A549, Calu1 and H460, respectively. Lung adenocarcinoma cell growth, proliferation, apoptosis, cell cycle in vitro and in vivo were then analyzed. DKK3 knockdown by siRNA transfection rendered A549, Calu1 and H460 resistant to cisplatin. As a result of DKK3 transfection, the expression of DKK3 and E-cadherin was significantly upregulated, while that of MMP7, survivin, c-myc and cyclin D1 was downregulated. DKK3 overexpression retarded cell proliferation, induced cell cycle arrest and apoptosis, and reduced cell invasive ability in the A549 and A549cis cells. In addition, the proportions of apoptotic cells and the PARP level were significantly increased in A549cis-and H460cis-DKK3 cells treated with cisplatin. Moreover, tumor growth was retarded more in cisplatin-treated nude mice seeded with A549cis-DKK3 cells than with A549cis cells. Cell viability increased with the pretreatment of SB216763 for 2 h in A549cis and A549cis-DKK3 cells incubated with cisplatin (1 µM) for 72 h. In conclusion, the re-activation of Dkk3 enhances the chemosensitivity to cisplatin in cisplatin-resistant lung adenocarcinoma cell lines, which requires additional studies to realize this potential in clinical use. IntroductionLung cancer has emerged as the third leading cause of cancer-related mortality worldwide (1). In the USA, over 200,000 new lung cancer cases are diagnosed annually, causing over 150,000 deaths in one year (1). Approximately 85% of lung cancer patients suffer from non-small cell lung cancer (NSCLC). Due to the comparative therapeutic advantage, cisplatin-based combination regimens are recommended as the optimal choice currently for the majority of NSCLC patients indicative of chemotherapy or adjuvant chemotherapy (2). However, the average survival time for patients with advanced stage of NSCLC receiving cisplatin plus gemcitabine treatment is ~16 months and may even be reduced to 12 months in those with cisplatin-resistance (3). The dilemma in managing late-stage NSCLC requires the elucidation of the mechanisms in cisplatin resistance to define novel, effective and applicable therapeutic targets for lung cancer (2,3).Several signal transduction pathways controlling chemosensitivity are aberrantly activated in various types of cancer, among which Wnt is of special significance (4). The role of Wnt1/Int-1 in the induction of mouse mammary tumor as an integration site for mouse mammary tumor virus (MMTV) was first recognized 30 years ago (4). Wnt/β-catenin signaling is initiated by the binding of secre...

show abstract

Section: Discussionmentioning

confidence: 99%

Dickkopf-3 (Dkk3) induces apoptosis in cisplatin-resistant lung adenocarcinoma cells via the Wnt/β-catenin pathway

Wang

et al. 2014

Oncology Reports

View full text Add to dashboard Cite

show abstract

“…Since, a relationship between β-catenin and Oct-4 was found in cancer cells and embryonic stem cells, it was evident that β-catenin might maintain the characteristics of cancer stem cells along with Oct-4 [10,7]. Previously, we have found a positive relationship and interaction between β-catenin and keratinocyte stem/progenitor cell marker ∆Np63 in maintaining proliferation of oral carcinoma cells [5].…”

Section: Introductionmentioning

confidence: 87%

“…Western blot and co-immunoprecipitation analysis were done in 16 cases including normal (6) and carcinoma (10). The protein lysates were prepared as described by Ratovitski et al [31] and immunoblotted as input control.…”

Section: Western Blot and Co-immunoprecipitationmentioning

confidence: 99%

Association of differential β‐catenin expression with Oct‐4 and Nanog in oral squamous cell carcinoma and their correlation with clinicopathological factors and prognosis

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Knockdown approaches now pervade cell biology and are emerging in therapeutics 28 , but biological variations in lamin-A,C have been reported as cancer biomarkers in patients, 29 during aging 9 and stem cell differentiation. 30 Here, lamin-A,C was partially knocked-down in a human lung cancer derived cell line (A549) that reportedly possesses some characteristics of cancer stem cells, 31 and it was knocked down in human MSCs. Our studies combine label-free mass spectrometry methods with an algorithm developed to identify optimal multi-peptide fingerprints by filtering out the distorting effects of incomplete trypsinization, peptides shared between isoforms, variable ionization, and overlapping signals.…”

Section: Introduction: Mass Spectrometry Uncovers Scaling Of Lamina Cmentioning

confidence: 97%

Label-free mass spectrometry exploits dozens of detected peptides to quantify lamins in wildtype and knockdown cells

Swift

Harada

Buxboim

et al. 2013

Nucleus

View full text Add to dashboard Cite

L abel-free quantitation and characterization of proteins by mass spectrometry (ms) is now feasible, especially for moderately expressed structural proteins such as lamins that typically yield dozens of tryptic peptides from tissue cells. using standard cell culture samples, we describe general algorithms for quantitative analysis of peptides identified in liquid chromatography tandem mass spectrometry (Lc-ms/ms). the algorithms were foundational to the discovery that the absolute stoichiometry of a-type to b-type lamins scales with tissue stiffness (swift et al., Science 2013). isoform dominance helps make sense of why mutations and changes with age of mechanosensitive lamin-a,c only affect "stiff" tissues such as heart, muscle, bone, or even fat, but not brain. a peak ratio fingerprinting (prf) algorithm is elaborated here through its application to lamin-a,c knockdown. after demonstrating the large dynamic range of prf using calibrated mixtures of human and mouse lysates, we validate measurements of partial knockdown with standard cell biology analyses using quantitative immunofluorescence and immunoblotting. optimal sets of ms-detected peptides as determined by prf demonstrate that the strongest peptide signals are not necessarily the most reliable for quantitation. after lamin-a,c knockdown, prf computes an invariant set of "housekeeping" proteins as part of a broader proteomic analysis that also shows the proteome of mesenchymal stem cells (mscs) is more broadly perturbed than that of a human epithelial cancer line (a549s), with particular variation in nuclear and cytoskeletal proteins. these methods offer exciting prospects for basic and clinical studies of lamin-a,c as well as other ms-detectable proteins.

show abstract

Wnt/β-catenin signaling regulates cancer stem cells in lung cancer A549 cells

Cited by 216 publications

References 28 publications

Dickkopf-3 (Dkk3) induces apoptosis in cisplatin-resistant lung adenocarcinoma cells via the Wnt/β-catenin pathway

Dickkopf-3 (Dkk3) induces apoptosis in cisplatin-resistant lung adenocarcinoma cells via the Wnt/β-catenin pathway

Association of differential β‐catenin expression with Oct‐4 and Nanog in oral squamous cell carcinoma and their correlation with clinicopathological factors and prognosis

Label-free mass spectrometry exploits dozens of detected peptides to quantify lamins in wildtype and knockdown cells

Contact Info

Product

Resources

About