NCAPH regulates gastric cancer progression through DNA damage response

Wang, Yan; Li, Junqiang; Yang, Zhiliang; Wang, Long; Sun, Yongfang; Li, Zi-Yue; Qin, Long

doi:10.4149/neo_2021_210607n761

Cited by 12 publications

(9 citation statements)

References 17 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, understanding the mechanism of COAD drug resistance is essential for improving patient survival. In recent years, abnormally expressed NCAPH has been found in breast cancer, endometrial cancer, NSCLC, and gastric cancer [24,30–32]. In this study, we found high expression of NCAPH in COAD, which was in line with the findings of Yin L et al [26].…”

Section: Discussionsupporting

confidence: 92%

FOXM1/NCAPH activates glycolysis to promote colon adenocarcinoma stemness and 5-FU resistance

et al. 2023

View full text Add to dashboard Cite

Chemotherapy using 5-fluorouracil (5-FU) is currently considered the most effective treatment for advanced colon adenocarcinoma (COAD). However, drug resistance remains a major obstacle in treating COAD. Non-SMC condensin I complex subunit H (NCAPH) is known to have a certain impact on the development of COAD, but its precise involvement in the mechanism of 5-FU resistance has not been demonstrated. Bioinformatics analysis was utilized to assay the expression of NCAPH and Forkhead box M1 (FOXM1) in COAD tumor tissues, which was then verified in COAD cell lines. The resistance of COAD cells to 5-FU was measured by CCK-8 assay, stemness was tested by cell sphere formation assay, and glycolysis ability was measured by cellular energy analysis metabolism. Chromatin Immunoprecipitation and dual-luciferase reporter assays were done to confirm the specific interaction between FOXM1 and NCAPH. The expression levels of FOXM1 and NCAPH were significantly upregulated in COAD tissues and cells, and they were involved in regulating the glycolytic signaling pathway. Inhibition of the glycolytic pathway could reverse the effect of NCAPH overexpression on COAD stemness and resistance. FOXM1 was identified as a transcription factor of NCAPH, and it regulated COAD glycolysis, cell stemness, and 5-FU resistance by activating NCAPH expression. FOXM1-mediated upregulation of NCAPH expression promoted COAD cell stemness and resistance via the glycolytic pathway. This study provides a possible mechanism for the FOXM1/NCAPH axis in the glycolytic pathway, cell stemness, and resistance in COAD.

show abstract

Section: Discussionsupporting

confidence: 92%

FOXM1/NCAPH activates glycolysis to promote colon adenocarcinoma stemness and 5-FU resistance

et al. 2023

View full text Add to dashboard Cite

show abstract

“…In the last ve years, high levels of NCAPH expression have been associated with the pathogenesis and prognosis of several tumor types (32)(33)(34)(35)(36)(37)(38)(39)(40), including hepatocarcinoma (41), lung tumors (42)(43)(44), melanoma (45), endometrial cancer(46) and hormone-dependent BC (22,47). Here, we demonstrate that NCAPH participates in the pathogenesis of BC in vivo and in vitro.…”

mentioning

confidence: 64%

A 10-gene signature associated with elevated levels of NCAPH identifies luminal A breast cancer patients with a risk of relapse

Mendiburu-Eliçabe

García-Sancha

Corchado-Cobos

et al. 2023

Preprint

View full text Add to dashboard Cite

Background Despite their generally favorable prognosis, luminal A tumors paradoxically pose the highest ten-year recurrence risk among breast cancers, with a quarter recurring within five years. Identifying such patients is crucial as long-term relapsers could benefit from extended hormone therapy, while early relapsers may require aggressive treatment. We propose a gene signature, sourced from genes such as NCAPH associated with luminal A breast cancer pathogenesis and poor prognosis, for improved stratification of these high-risk patients. Methods We used in vitro and in vivo mouse models to study the implication of NCAPH in breast cancer progression. We performed transcriptomic analysis from a backcross cohort of mice with breast tumors. Transcripts that were associated with high intratumoral Ncaph levels were used for a LASSO multivariate regression model in the human databases. Results We demonstrated that NCAPH participates in the pathogenesis of luminal breast cancer in vitro and in vivo using different mouse models. Transgenic mice overexpressing NCAPH generated breast tumors with a long latency, and in MMTV-NCAPHErbB2+ double-transgenic mice, the luminal tumors formed were more aggressive. In addition, high levels of Ncaph were associated with worse evolution and a poor response to chemotherapy in a cohort of genetically heterogeneous transgenic mice generated by backcrossing. Moreover, NCAPH levels were higher in patients with poor long-term evolution. Using LASSO multivariate regression, we identified a ten-gene risk score formed by a gene signature (Gene Signature for Luminal A 10 or GSLA10) that correlated with high intratumoral NCAPH expression and poor luminal A breast cancer evolution. This GSLA10 signature outperforms the Oncotype DX signature in distinguishing tumors with a poor outcome (previously categorized as luminal A by PAM50) in three independent human cohorts. Conclusions The GSLA10 signature assists in identifying patients with luminal A tumors exhibiting poor prognosis, who could thus potentially benefit from personalized treatment strategies.

show abstract

“…[81][82][83][84][85][86] with worse outcome are thought to have higher genomic instability, alterations to P53 19 and overexpression of genes that regulate mitosis. 20 In the last 5 years, high levels of NCAPH expression have been associated with the pathogenesis and prognosis of several tumour types, 81,82,84,[86][87][88][89][90][91] including hepatocarcinoma, 92 lung tumours, 93-95 melanoma 96 and endometrial cancer. 83 During the development of this project, two studies on NCAPH in breast cancer were published.…”

Section: Discussionmentioning

confidence: 99%

“…In the last 5 years, high levels of NCAPH expression have been associated with the pathogenesis and prognosis of several tumour types, 81 , 82 , 84 , 86 , 87 , 88 , 89 , 90 , 91 including hepatocarcinoma, 92 lung tumours, 93 , 94 , 95 melanoma 96 and endometrial cancer. 83 During the development of this project, two studies on NCAPH in breast cancer were published.…”

Section: Discussionmentioning

confidence: 99%

NCAPH drives breast cancer progression and identifies a gene signature that predicts luminal a tumour recurrence

Mendiburu‐Eliçabe,

García‐Sancha,

Corchado‐Cobos

et al. 2024

Clinical & Translational Med

View full text Add to dashboard Cite

BackgroundLuminal A tumours generally have a favourable prognosis but possess the highest 10‐year recurrence risk among breast cancers. Additionally, a quarter of the recurrence cases occur within 5 years post‐diagnosis. Identifying such patients is crucial as long‐term relapsers could benefit from extended hormone therapy, while early relapsers might require more aggressive treatment.MethodsWe conducted a study to explore non‐structural chromosome maintenance condensin I complex subunit H’s (NCAPH) role in luminal A breast cancer pathogenesis, both in vitro and in vivo, aiming to identify an intratumoural gene expression signature, with a focus on elevated NCAPH levels, as a potential marker for unfavourable progression. Our analysis included transgenic mouse models overexpressing NCAPH and a genetically diverse mouse cohort generated by backcrossing. A least absolute shrinkage and selection operator (LASSO) multivariate regression analysis was performed on transcripts associated with elevated intratumoural NCAPH levels.ResultsWe found that NCAPH contributes to adverse luminal A breast cancer progression. The intratumoural gene expression signature associated with elevated NCAPH levels emerged as a potential risk identifier. Transgenic mice overexpressing NCAPH developed breast tumours with extended latency, and in Mouse Mammary Tumor Virus (MMTV)‐NCAPHErbB2 double‐transgenic mice, luminal tumours showed increased aggressiveness. High intratumoural Ncaph levels correlated with worse breast cancer outcome and subpar chemotherapy response. A 10‐gene risk score, termed Gene Signature for Luminal A 10 (GSLA10), was derived from the LASSO analysis, correlating with adverse luminal A breast cancer progression.ConclusionsThe GSLA10 signature outperformed the Oncotype DX signature in discerning tumours with unfavourable outcomes, previously categorised as luminal A by Prediction Analysis of Microarray 50 (PAM50) across three independent human cohorts. This new signature holds promise for identifying luminal A tumour patients with adverse prognosis, aiding in the development of personalised treatment strategies to significantly improve patient outcomes.

show abstract

NCAPH regulates gastric cancer progression through DNA damage response

Cited by 12 publications

References 17 publications

FOXM1/NCAPH activates glycolysis to promote colon adenocarcinoma stemness and 5-FU resistance

FOXM1/NCAPH activates glycolysis to promote colon adenocarcinoma stemness and 5-FU resistance

A 10-gene signature associated with elevated levels of NCAPH identifies luminal A breast cancer patients with a risk of relapse

NCAPH drives breast cancer progression and identifies a gene signature that predicts luminal a tumour recurrence

Contact Info

Product

Resources

About