Association of EGFR and KRAS mutations with expression of p-AKT, DR5 and DcR1 in non-small cell lung cancer

Zhao, Xudong; Deng, Hong-Bin; Lu, Chenyu; Bao, Yuanyuan; Lu, Xuesong; Deng, Ling

doi:10.4149/neo_2017_203

Cited by 11 publications

(5 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, we found LPCAT1 was highly expressed in A549 and H460 cells compared with the normal human bronchial epithelial cell line Beas-2B. Moreover, KRAS gene is an important downstream molecule in the EGFR signal transduction pathway [51], and KRAS is involved in proper stimulation of PI3K signaling cascade [52]. Previous studies also found that the expression of AKT and p-AKT was significantly higher in NSCLC tissue with KRAS mutation compared to those with wild-type KRAS [51, 53].…”

Section: Discussionmentioning

confidence: 99%

LPCAT1 promotes brain metastasis of lung adenocarcinoma by up-regulating PI3K/AKT/MYC pathway

Wei

Dong

Lü

et al. 2019

J Exp Clin Cancer Res

116

View full text Add to dashboard Cite

Background Brain metastasis (BM) is associated with poor prognosis, recurrence, and death in patients with non-small cell lung cancer (NSCLC). Lysophosphatidylcholine acyltransferase 1 (LPCAT1) has been reported to be involved in the progression, metastasis and recurrence of malignancies. However, the potential role of LPCAT1 in NSCLC remains poorly understood. This study was aimed to identify genes involved in lung adenocarcinoma (LUAD) brain metastasis, and look into the role of LPCAT1 in LUAD progression. Methods We used integrative genomic analysis to identify genes involved in lung adenocarcinomas. LPCAT1 expression was evaluated in tumor tissues from LUAD patients and LUAD cell lines. The role of LPCAT1 was subsequently investigated both in vitro and in vivo. The mechanism underlying the involvement of LPCAT1 in LUAD progression was explored with the activator of PI3K/AKT pathway. RNA sequencing was performed to confirm the involvement of LPCAT1 and associated pathway in LUAD brain metastasis. Results LPCAT1 was up-regulated in LUAD tissues and cell lines. shRNA-mediated depletion of LPCAT1 not only abrogated cell proliferation, migration and invasion in vitro, but also arrested tumor growth and brain metastases in vivo. Notably, LPCAT1 at least partially influenced LUAD progression through PI3K/AKT signal pathway by targeting MYC transcription. Moreover, expression of LPCAT1 was higher in tissues of LUAD patients with BM than those without BM as revealed by IHC staining, RNA-Sequencing and qPCR analysis. Finally, elevated LPCAT1 expression in patients with lung adenocarcinomas was associated with a poor clinical outcome. Conclusions This study showed that LPCAT1 works as a regulator of cell metastasis and may serve as a novel therapeutic target for BM in lung adenocarcinoma. Electronic supplementary material The online version of this article (10.1186/s13046-019-1092-4) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

LPCAT1 promotes brain metastasis of lung adenocarcinoma by up-regulating PI3K/AKT/MYC pathway

Wei

Dong

Lü

et al. 2019

J Exp Clin Cancer Res

116

View full text Add to dashboard Cite

show abstract

“…This indicates that EGFR mutation can activate the downstream PI3K/AKT/mTOR signaling pathway, and lead to the overexpression of AKT and p-AKT, thereby promoting the development of lung cancer. Previous studies (16,21,22) have found that the expression of p-AKT in NSCLC is closely related to poor differentiation and lymph node metastasis, and it is believed that the activation of AKT plays an important role in the development of lung cancer. Other studies, however, have observed the opposite effect.…”

Section: Discussionmentioning

confidence: 99%

“…The present study revealed that the positive staining of AKT and p-AKT was observed predominantly in the cytoplasm and occasionally in the nucleus. AKT is overexpressed in various types of human cancer such as lung cancer, breast cancer, and prostate cancer (12,13,16,17). Previous studies have reported positive rates of AKT between 52.1% and 93.3% (13,18,19) and positive rates of p-AKT between 33.3% and 87.5% (13,(20)(21)(22).…”

Section: Discussionmentioning

confidence: 99%

Expression of AKT and p-AKT protein in lung adenocarcinoma and its correlation with PD-L1 protein and prognosis

Hu¹,

Huang²,

Zhang³

et al. 2020

Ann Transl Med

View full text Add to dashboard Cite

Background: The PI3K/AKT/mTOR signaling pathway were significantly associated with EGFR mutation in lung adenocarcinoma (LUAD), but its correlation with PD-L1 protein and prognosis are not clear. The aim of this study was to evaluate the expression of AKT and phosphorylated AKT (p-AKT) in LUAD and its correlation with programmed death ligand-1 (PD-L1); and to analyze the factors affecting LUAD prognosis.Methods: The expression of AKT, p-AKT, and PD-L1 was examined using immunohistochemistry in LUAD tissues from 110 patients who underwent surgical treatment. Results: AKT protein expression was examined in 64.5% (71/110) of the LUAD samples, and p-AKT protein expression was examined in 44.5% (49/110) of the LUAD samples. The positive rate of PD-L1 at TC1/2/3 was 38.2% (42/110). AKT and p-AKT expression was significantly associated with epidermal growth factor receptor (EGFR) mutation (P=0.016, P=0.014 respectively). Pearson's correlation analysis indicated a negative correlation of p-AKT with PD-L1 protein (P=0.022). Out of the 62 patients with EGFR mutation, the expression of PD-L1 was negatively correlated with that of p-AKT protein (P=0.032).The expressions of AKT and p-AKT were not associated with prognosis. Multivariate analysis showed that tumor-node-metastasis (TNM) stage (P=0.013) and differentiation (P=0.046) were independent prognostic factors for overall survival.

show abstract

“…PTEN participates in growth inhibition, apoptosis promotion, cell cycle regulation, inhibition of cell adhesion and tumor metastasis by regulating the PIP3 pathway (Nosaka, Yamasaki et al 2017, Wise, Hermida et al 2017). The gene deletion and inactivation of PTEN or the over-expression of PIP3 can convert Akt to p-Akt (Zhao, Deng et al 2017). P-Akt acts on downstream mTOR and other substrates through a phosphorylation cascade to promote tumor proliferation and angiogenesis, as well as accelerate tumor invasion and metastasis (Manning and Toker 2017).…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance and molecular mechanisms of LPCAT1 in lung squamous cell carcinoma

Shi,

Zeng,

Zha

et al. 2024

Preprint

View full text Add to dashboard Cite

LPCAT1 acts as an oncogene in a variety of cancers, but its effect on lung squamous cell carcinoma (LUSC) has not been reported. This study aimed to determine the prognostic value of LPCAT1 by bioinformatics analyses and to confirm its effect on LUSC cell functions by in vitroexperiments. The expression data and clinical information were obtained from the public database. The prognostic value of LPCAT1 was evaluated by Kaplan-Meier curves, nomogram analysis, and Cox regression analyses. The relationships of LPCAT1 and immune features were also estimated. Then, expressions of LPCAT1 and PTEN/Akt pathway in LUSC cell lines (NCI-H226 and NCI-H520) were detected by real-time quantitative polymerase chain reaction and western blot. Cell viability, invasion, and apoptosis were evaluated by CCK-8 assay, Transwell assay, and flow cytometry, respectively. The bioinformatics analyses suggested that LPCAT1 is an independent prognostic risk factor of LUSC and has predictive potential. Meanwhile, LPCAT1 was significantly associated with immune cell infiltration and immune checkpoint gene expressions. Experiment data suggested that LPCAT1 can promote proliferation and invasion but inhibit apoptosis in LUSC cell lines. LPCAT1 can also significantly decrease the PTEN expression but increase the p-Akt expression in vitro. LPCAT1 indicates prognosis and correlates with immune features in LUSC. Experiment data indicated that LPCAT1 may promote proliferation and invasion but inhibit apoptosis of LUSC cell lines via the PTEN/Akt pathway.

show abstract

Association of EGFR and KRAS mutations with expression of p-AKT, DR5 and DcR1 in non-small cell lung cancer

Cited by 11 publications

References 26 publications

LPCAT1 promotes brain metastasis of lung adenocarcinoma by up-regulating PI3K/AKT/MYC pathway

LPCAT1 promotes brain metastasis of lung adenocarcinoma by up-regulating PI3K/AKT/MYC pathway

Expression of AKT and p-AKT protein in lung adenocarcinoma and its correlation with PD-L1 protein and prognosis

Prognostic significance and molecular mechanisms of LPCAT1 in lung squamous cell carcinoma

Contact Info

Product

Resources

About