Anti‐tumour effects of Keratin 6A in lung adenocarcinoma

Xiao, Jian; Xiao, Kun; Dai, Longxia; Zhang, Lihai; He, Bixiu

doi:10.1111/crj.13182

Cited by 9 publications

(7 citation statements)

References 31 publications

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“…Through clinical analysis, we found that the elevated expression of KRT6A can be used as a risk factor for predicting the survival outcome of NSCLC patients. Interestingly, another study confirmed our finding by showing that KRT6A inhibits the proliferation and invasion of lung adenocarcinoma cells, and high expression of KRT6A protein may be a prognostic marker for patients with lung adenocarcinoma ( Xiao et al, 2020 ). Therefore, deeper investigations are warranted to explore the function of KRT6A in lung cancer progression.…”

Section: Discussionsupporting

confidence: 82%

KRT6A Promotes Lung Cancer Cell Growth and Invasion Through MYC-Regulated Pentose Phosphate Pathway

Che

Wang

Sun

et al. 2021

Front. Cell Dev. Biol.

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Keratin 6A (KRT6A) belongs to the keratin protein family which is a critical component of cytoskeleton in mammalian cells. Although KRT6A upregulation in non-small cell lung cancer (NSCLC) has been reported, the regulatory mechanism and functional role of KRT6A in NSCLC development have been less well investigated. In this study, KRT6A was confirmed to be highly expressed in NSCLC tissue samples, and its high expression correlated with poor patient prognosis. Furthermore, overexpression of KRT6A promotes NSCLC cell proliferation and invasion. Mechanistically, KRT6A overexpression is sufficient to upregulate glucose-6-phosphate dehydrogenase (G6PD) levels and increase the pentose phosphate pathway flux, an essential metabolic pathway to support cancer cell growth and invasion. In addition, we discovered that lysine-specific demethylase 1A (LSD1) functions upstream to promote KRT6A gene expression. We also found that the MYC family members c-MYC/MYCN are involved in KRT6A-induced G6PD upregulation. Therefore, this study reveals an underappreciated mechanism that KRT6A acts downstream of LSD1 and functions as a pivotal driver for NSCLC progression by upregulating G6PD through the MYC signaling pathway. Together, KRT6A and LSD1 may serve as potential prognostic indictors and therapeutic targets for NSCLC.

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Section: Discussionsupporting

confidence: 82%

KRT6A Promotes Lung Cancer Cell Growth and Invasion Through MYC-Regulated Pentose Phosphate Pathway

Che

Wang

Sun

et al. 2021

Front. Cell Dev. Biol.

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“…Additionally, LAMC2 promotes the chemotactic function of granulocytes ( 53 , 54 ); DSC2 correlates positively with adhesion, migration, and infiltration of granulocytes ( 55 , 56 ); and KRT6A protein inhibits the proliferation, migration and invasion abilities of lung cancer cells. The high expression of KRT6A protein is related to good prognosis in patients with lung adenocarcinoma ( 57 ); FOSB protein plays an anti-tumor role in lung cancer ( 58 ). These results indicated that ginsenoside Rg1 significantly inhibited the mRNA expression of ARG2, MMP1, S100A4 , and RAPSN in granulocytes inhibited by NA and, simultaneously, significantly elevated the mRNA expression of LAMC2, DSC2, KRT6A , and FOSB .…”

Section: Resultsmentioning

confidence: 99%

“…The peptides from the C-terminal region of the protein show antimicrobial activity against bacterial pathogens. KRT6A protein inhibits the proliferation, migration and invasion abilities of lung adenocarcinoma cells, and high expression of KRT6A protein is a predictor of good prognosis in patients with lung adenocarcinoma ( 57 ). Neutrophils could directly kill tumor cells by releasing NO ( 84 ).…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg1 as a promising adjuvant agent for enhancing the anti-cancer functions of granulocytes inhibited by noradrenaline

Zhu

Chen

et al. 2023

Front. Immunol.

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IntroductionIn recent years, numerous studies have confirmed that chronic stress is closely related to the development of cancer. Our previous research showed that high levels of stress hormones secreted in the body during chronic stress could inhibit the cancer-killing activity of granulocytes, which could further promote the development of cancer. Therefore, reversing the immunosuppressive effect of stress hormones on granulocytes is an urgent problem in clinical cancer treatment. Here, we selected noradrenaline (NA) as a representative stress hormone.Methods and resultsAfter screening many traditional Chinese herbal medicine active ingredients, a promising compound, ginsenoside Rg1, attracted our attention. We verified the immunoprotective effect of ginsenoside Rg1 on granulocytes in vitro and ex vivo, and attempted to understand its potential immunoprotective mechanism. We confirmed the immunoprotective effect of ginsenoside Rg1 on granulocytes using cell and animal experiments. Cell counting kit-8 (CCK-8) and ex vivo experiments were performed to investigate the immunoprotective effects of ginsenoside Rg1 on the anti-cancer function of granulocytes inhibited by NA. Transcriptome sequencing analysis and qRT-PCR showed that NA elevated the mRNA expression of ARG2, MMP1, S100A4, and RAPSN in granulocytes, thereby reducing the anti-cancer function of granulocytes. In contrast, ginsenoside Rg1 downregulated the mRNA expression of ARG2, MMP1, S100A4, and RAPSN, and upregulated the mRNA expression of LAMC2, DSC2, KRT6A, and FOSB, thereby enhancing the anti-cancer function of granulocytes inhibited by NA. Transwell cell migration experiments were performed to verify that ginsenoside Rg1 significantly enhanced the migration capability of granulocytes inhibited by NA. Tumor-bearing model mice were used to verify the significant immunoprotective effects in vivo. Finally, CCK-8 and hematoxylin and eosin staining experiments indicated that ginsenoside Rg1 exhibited high biosafety in vitro and in vivo.DiscussionIn future clinical treatments, ginsenoside Rg1 may be used as an adjuvant agent for cancer treatment to alleviate chronic stress-induced adverse events in cancer patients.

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“…Silencing KRT6A has been demonstrated to inhibit invasion and metastasis in nasopharyngeal cancers [34]. However, its role in lung adenocarcinoma is somewhat ambiguous, with varying reports suggesting that it may act as both an oncogene and a tumor suppressor [34,35].…”

Section: Discussionmentioning

confidence: 99%

Six-Gene Signature for Differential Diagnosis and Therapeutic Decisions in Non-Small-Cell Lung Cancer—A Validation Study

Charkiewicz,

Sulewska,

Karabowicz

et al. 2024

IJMS

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Non-small-cell lung cancer (NSCLC) poses a challenge due to its heterogeneity, necessitating precise histopathological subtyping and prognostication for optimal treatment decision-making. Molecular markers emerge as a potential solution, overcoming the limitations of conventional methods and supporting the diagnostic–therapeutic interventions. In this study, we validated the expression of six genes (MIR205HG, KRT5, KRT6A, KRT6C, SERPINB5, and DSG3), previously identified within a 53-gene signature developed by our team, utilizing gene expression microarray technology. Real-time PCR on 140 thoroughly characterized early-stage NSCLC samples revealed substantial upregulation of all six genes in squamous cell carcinoma (SCC) compared to adenocarcinoma (ADC), regardless of clinical factors. The decision boundaries of the logistic regression model demonstrated effective separation of the relative expression levels between SCC and ADC for most genes, excluding KRT6C. Logistic regression and gradient boosting decision tree classifiers, incorporating all six validated genes, exhibited notable performance (AUC: 0.8930 and 0.8909, respectively) in distinguishing NSCLC subtypes. Nevertheless, our investigation revealed that the gene expression profiles failed to yield predictive value regarding the progression of early-stage NSCLC. Our molecular diagnostic models manifest the potential for an exhaustive molecular characterization of NSCLC, subsequently informing personalized treatment decisions and elevating the standards of clinical management and prognosis for patients.

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Anti‐tumour effects of Keratin 6A in lung adenocarcinoma

Cited by 9 publications

References 31 publications

KRT6A Promotes Lung Cancer Cell Growth and Invasion Through MYC-Regulated Pentose Phosphate Pathway

KRT6A Promotes Lung Cancer Cell Growth and Invasion Through MYC-Regulated Pentose Phosphate Pathway

Ginsenoside Rg1 as a promising adjuvant agent for enhancing the anti-cancer functions of granulocytes inhibited by noradrenaline

Six-Gene Signature for Differential Diagnosis and Therapeutic Decisions in Non-Small-Cell Lung Cancer—A Validation Study

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