Modification of platinum sensitivity by KEAP1/NRF2 signals in non-small cell lung cancer

Tian, Yijun; Wu, Kongming; Liu, Qian; Han, Na; Zhang, Li; Chu, Qian; Yuan, Caixia

doi:10.1186/s13045-016-0311-0

Cited by 50 publications

(41 citation statements)

References 54 publications

(65 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tian et al . found that modification of Nrf2 and Keap1 expression changed cancer cell line sensitivity to platinum‐based drugs . Lee et al .…”

Section: Discussionmentioning

confidence: 99%

“…Aberrant signaling via the Keap1‐Nrf2 pathway frequently occurs in cancer cells, leading to the over‐activation of Nrf2 and elevation of ROS scavenging ability, facilitating the initiation and development of malignant cells that produce ROS during rapid proliferation . On the other hand, ROS are also indispensable for the therapeutic effect of platinum complexes, fluorouracil, and X‐ray, which means that Nrf2 over‐activation could also help cancer cells survive chemotherapy and irradiation and subsequently relapse …”

Section: Introductionmentioning

confidence: 99%

“…The promoting role of aberrant Keap1‐Nrf2 signaling in carcinogenesis and therapy resistance has been well demonstrated in vivo and animal models; however, relevant clinical studies remain inadequate. Moreover, Keap1/Nrf2 expression in normal tissues has rarely been reported.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Nrf2 and Keap1 abnormalities in esophageal squamous cell carcinoma and association with the effect of chemoradiotherapy

et al. 2018

View full text Add to dashboard Cite

BackgroundThe Keap1‐Nrf2 pathway is a key antioxidant and redox signaling cascade. Pathway abnormalities enhance the reactive oxygen species scavenging ability of cancer cells; thus the pathway is involved in carcinogenesis and resistance to chemoradiotherapy (CRT). This retrospective study was conducted to examine the status of the Keap1‐Nrf2 pathway in locally advanced esophageal squamous cell carcinoma (ESCC) and to analyze its prognostic value in patients receiving CRT.MethodsNrf2 and Keap1 expression were immunohistochemically examined in 152 ESCC and 31 normal esophageal mucosae. All ESCC specimens were obtained from patients with locally advanced ESCC who underwent CRT.ResultsStrong staining of nuclear and cytoplasmic Nrf2 and limited or absent Keap1 expression was uncommon in normal tissues, but frequently observed in ESCC. Interaction between Nrf2 and Keap1 in normal mucosae is negatively correlated, while in tumors there is no negative correlation, indicating that there is little to no interaction between Nrf2 and Keap1 in ESCC. Positive Nrf2 expression in the nucleus was of diagnostic value for predicting ESCC from normal esophageal mucosae, and was significantly associated with poorer clinical response and poor progression‐free survival after CRT. The value of Keap1 expression for diagnosis and predicting CRT outcomes was marginal. These different influences of Keap1 and Nrf2 on ESCC indicated that the signaling of this pathway was disturbed and displayed a Keap1‐independent pattern.ConclusionAberrant signaling via the Keap1‐Nrf2 pathway was common in ESCC and was associated with response and survival after CRT.

show abstract

“…Tian et al . found that modification of Nrf2 and Keap1 expression changed cancer cell line sensitivity to platinum‐based drugs . Lee et al .…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Nrf2 and Keap1 abnormalities in esophageal squamous cell carcinoma and association with the effect of chemoradiotherapy

et al. 2018

View full text Add to dashboard Cite

show abstract

“…For example, novel agents targeting epidermal growth factor receptor (EGFR) mutation and echinoderm microtubule-associated protein-like anaplastic lymphoma kinase (EML4-ALK) fusion benefit the patients with advanced ADC [22, 23]. Other molecular alterations, such as Notch signaling, NLK, and NRF2, also contribute to NSCLC progression [24–26]. Accordingly, exploring new molecular markers is conducive to precision treatment.…”

Section: Discussionmentioning

confidence: 99%

The expression profile and clinic significance of the SIX family in non-small cell lung cancer

Liu

Tian

et al. 2016

J Hematol Oncol

Self Cite

View full text Add to dashboard Cite

BackgroundThe SIX family homeobox genes have been demonstrated to be involved in the tumor initiation and progression, but their clinicopathological features and prognostic values in non-small cell lung cancer (NSCLC) have not been well defined. We analyzed relevant datasets and performed a systemic review and a meta-analysis to assess the profile of SIX family members in NSCLC and evaluate their importance as biomarkers for diagnosis and prediction of NSCLC.MethodsThis meta-analysis included 17 studies with 2358 patients. Hazard ratio (HR) and 95 % confidence interval (CI) were calculated to represent the prognosis of NSCLC with expression of the SIX family genes. Heterogeneity of the ORs and HRs was assessed and quantified using the Cochrane Q and I 2 test. Begg’s rank correlation method and Egger’s weighted regression method were used to screen for potential publication bias. Bar graphs of representative datasets were plotted to show the correlation between the SIX expression and clinicopathological features of NSCLC. Kaplan-Meier survival curves were used to validate our prognostic analysis by pooled HR.ResultsThe systematic meta-analysis unveiled that the higher expressions of SIX1-5 were associated with the greater possibility of the tumorigenesis. SIX4 and SIX6 were linked to the lymph node metastasis (LNM). SIX2, SIX3, and SIX4 were correlated with higher TNM stages. Furthermore, the elevated expressions of SIX2, SIX4, and SIX6 predicted poor overall survival (OS) in NSCLC (SIX2: HR = 1.14, 95 % CI, 1.00–1.31; SIX4: HR = 1.39, 95 % CI, 1.16–1.66; SIX6: HR = 1.18, 95 % CI, 1.00–1.38) and poor relapse-free survival (RFS) in lung adenocarcinoma (ADC) (SIX2: HR = 1.42, 95 % CI, 1.14–1.77; SIX4: HR = 1.52, 95 % CI, 1.09–2.11; SIX6: HR = 1.25, 95 % CI, 1.01–1.56).ConclusionsOur report demonstrated that the SIX family members play distinct roles in the tumorigenesis of NSCLC and can be potential biomarkers in predicting prognosis of NSCLC patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-016-0339-1) contains supplementary material, which is available to authorized users.

show abstract

“…Western blot assay was performed following the protocol as previously described [24, 25]. Briefly, the cells were harvested and lysed using ice-cold RIPA lysis buffer (50 mM Tris-HCl (pH 7.4), 150 mM sodium chloride, 1% Nonidet P-40, and 0.5% sodium deoxycholate).…”

Section: Methodsmentioning

confidence: 99%

Prognostic and therapeutic value of disruptor of telomeric silencing-1-like (DOT1L) expression in patients with ovarian cancer

Zhang

Liu

et al. 2017

J Hematol Oncol

View full text Add to dashboard Cite

BackgroundEpigenetics has been known to play a critical role in regulating the malignant phenotype. This study was designed to examine the expression of DOT1L (histone 3 lysine 79 methyltransferase) and H3K79 methylation in normal ovarian tissues and ovarian tumors and to explore the function of DOT1L and its underline mechanisms in ovarian cancer.MethodsThe expression of DOT1L and H3K79 methylation in 250 ovarian tumor samples and 24 normal ovarian samples was assessed by immunohistochemistry. The effects of DOT1L on cell proliferation in vitro were evaluated using CCK8, colony formation and flow cytometry. The DOT1L-targeted genes were determined using chromatin immune-precipitation coupled with high-throughput sequencing (ChIP-seq) and ChIP-PCR. Gene expression levels were measured by real-time PCR and immunoblotting. The effects of DOT1L on tumor growth in vivo were evaluated using an orthotopic ovarian tumor model.ResultsDOT1L expression and H3K79 methylation was significantly increased in malignant ovarian tumors. High DOT1L expression was associated with International Federation of Gynecology and Obstetrics (FIGO) stage, histologic grade, and lymphatic metastasis. DOT1L was an independent prognostic factor for the overall survival (OS) and progression-free survival (PFS) of ovarian cancer, and higher DOT1L expression was associated with poorer OS and PFS. Furthermore, DOT1L regulates the transcription of G1 phase genes CDK6 and CCND3 through H3K79 dimethylation; therefore, blocking DOT1L could result in G1 arrest and thereby impede the cell proliferation in vitro and tumor growth in vivo.ConclusionsOur findings first demonstrate that DOT1L over-expression has important clinical significance in ovarian cancer and also clarify that it drives cell cycle progression through transcriptional regulation of CDK6 and CCND3 through H3K79 methylation, suggesting that DOT1L might be potential target for prognostic assessment and therapeutic intervention in ovarian cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-017-0400-8) contains supplementary material, which is available to authorized users.

show abstract

Modification of platinum sensitivity by KEAP1/NRF2 signals in non-small cell lung cancer

Cited by 50 publications

References 54 publications

Nrf2 and Keap1 abnormalities in esophageal squamous cell carcinoma and association with the effect of chemoradiotherapy

Nrf2 and Keap1 abnormalities in esophageal squamous cell carcinoma and association with the effect of chemoradiotherapy

The expression profile and clinic significance of the SIX family in non-small cell lung cancer

Prognostic and therapeutic value of disruptor of telomeric silencing-1-like (DOT1L) expression in patients with ovarian cancer

Contact Info

Product

Resources

About