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
6171 - Molecular EGFR/PD-L1 profile of glioblastoma: Hints for therapeutic strategies
Presenter: Wojciech Szopa
Session: Poster Display session 1
Resources:
Abstract
4418 - Role of Intraoperative MRI (iMRI) in neurosurgery, potential imaging tool for maximizing gross total resection (GTR) rate of CNS tumours.
Presenter: Shweta Wadhwa
Session: Poster Display session 1
Resources:
Abstract
4791 - Tumor related impairments of neurocognitive functions in patients with brain metastases
Presenter: Lei Wen
Session: Poster Display session 1
Resources:
Abstract
5372 - Is radiation therapy influencing Alzheimer’s in Brain and Head and Neck Cancers?
Presenter: Anas Saad
Session: Poster Display session 1
Resources:
Abstract
2329 - Mature Treatment Results of 120 Cases of Acoustic Neuroma Treated with Cyberknife at a single institution.
Presenter: Shawn Malone
Session: Poster Display session 1
Resources:
Abstract
3207 - A phase II/III trial of high-dose, intermittent sunitinib in patients with recurrent glioblastoma: the STELLAR study
Presenter: Cyrillo Brahm
Session: Poster Display session 1
Resources:
Abstract
3589 - CNS penetration and Preliminary Efficacy of Sacutizumab Govitecan in Breast Brain Metastasis and Glioblastoma: A Surgical Study
Presenter: Andrew Brenner
Session: Poster Display session 1
Resources:
Abstract
1969 - Wedge resection with omission of lymph node dissection as an optional treatment strategy in octogenarians or older with early stage non-small cell lung cancers
Presenter: Takahiro Mimae
Session: Poster Display session 1
Resources:
Abstract
5116 - Characterization of lung tumorspheres reveals cancer stem-like cells potential targets and prognostic markers in non-small cell lung cancer
Presenter: Alejandro Herreros Pomares
Session: Poster Display session 1
Resources:
Abstract
5823 - Pulmonary tumor-draining vein exosomal lincRNA-p21 levels impacts non-small cell lung cancer prognosis
Presenter: Joan Castellano
Session: Poster Display session 1
Resources:
Abstract