Abstract 5011
Background
Aberrantly overexpressed lung cancer stem cell associated factor-X (LCSCAFX) has been implicated in non-small cell lung cancer (NSCLC) development.
Methods
To explore the effect of LCSCAFXon the lung cancer stem-like traitsin vitro and in vivo.
Results
We reported that enforced expression of LCSCAFX promoted NSCLC cells invasion and metastasis, drug resistance and recurrencein vitro and in vivo, whereas depletion of LCSCAFX suppressed metastasis and relapse in NSCLC. Moreover, we found that LCSCAFX expression was elevated in lung cancer stem cells (LCSCs). Indeed, knockdown of LCSCAFX impaired lung cancer stem-like traits. Conversely, ectopic overexpression of LCSCAFX enhanced the self-renewal ability of lung cancer cells in vitro. In addition, elevated LCSCAFX robustly enhanced tumor initiating frequencies, as well as growth rates of NSCLC cells derived tumor xenografts in immunodeficient mice. Furthermore, mechanistic investigations established that LCSCAFX stabilized c-Myc protein by suppressing its ubiquitylation and proteasomal degradation, which is required for lung cancer stem-like properties maintenance. Consistently, immunohistochemical analysis of clinical lung tumor tissues showed that LCSCAFX was elevated in NSCLC tissues and high LCSCAFX expression serve as an independent prognostic marker in patients with NSCLC. Importantly, genetic depletion of LCSCAFX combined chemotherapy dramatically inhibited NSCLC progression in patient-derived xenograft (PDX) model.
Conclusions
These findings demonstrated a previously unappreciated role of LCSCAFX in the regulation of LCSCs, assigning LCSCAFX as a promising therapeutic target for lung cancer treatments.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2304 - Synthetic peptide of tumor–associated antigen L6 formulated with polymer-based adjuvant enhances anti-tumor effects in mice
Presenter: Shih-jen Liu
Session: Poster Display session 1
Resources:
Abstract
4419 - Improving detection level of somatic mosaicism in neurofibromatosis type 1
Presenter: Kristina Karandasheva
Session: Poster Display session 1
Resources:
Abstract
5283 - Preclinical pharmacokinetic/pharmacodynamic (PK/PD) relationship of ABN401, a highly selective Met inhibitor, in gastric and non-small-cell lung cancer models
Presenter: JooSeok Kim
Session: Poster Display session 1
Resources:
Abstract
5488 - Transcription factors of Snail family in the regulation of resistance of breast cancer cells to hypoxic conditions
Presenter: Alvina Khamidullina
Session: Poster Display session 1
Resources:
Abstract
5417 - Metastasis is impaired by endothelial-specific Dll4 loss-of-function through inhibition of epithelial-to-mesenchymal transition and reduction of cancer stem cells and circulating tumour cells
Presenter: Liliana Mendonça
Session: Poster Display session 1
Resources:
Abstract
5494 - Identification of novel and known FGFR gene fusions in Chinese non-small cell lung cancer
Presenter: Weixin Zhao
Session: Poster Display session 1
Resources:
Abstract
3412 - WNT pathway mutations (APC/CTNNB1) and immune checkpoint inhibitors (ICI) response in metastatic non-small cell lung cancer (NSCLC) patients.
Presenter: Francisco Javier Ros Montana
Session: Poster Display session 1
Resources:
Abstract
1815 - Leukocytosis as a negative prognostic factor in patients with lung cancer: Which subpopulation of leukocytes is responsible?
Presenter: Filip Kohutek
Session: Poster Display session 1
Resources:
Abstract
5022 - Identification of MET gene amplifications using next-generation sequencing in non-small cell lung cancer patients
Presenter: Sergi Clavé
Session: Poster Display session 1
Resources:
Abstract
4925 - Prognostic role of CD73 in metastatic Non Small Cell Lung Cancer according to the presence of driver alterations
Presenter: Giulia Galli
Session: Poster Display session 1
Resources:
Abstract