Aldehyde dehydrogenase 3A1 activation prevents radiation-induced xerostomia by protecting salivary stem cells from toxic aldehydes

Saiki, Julie; Cao, Hongbin; Wassenhove, Lauren D. Van; Viswanathan, Vignesh; Bloomstein, Joshua; Nambiar, Dhanya K.; Mattingly, Aaron; Jiang, Dadi; Chen, Che Hong; Stevens, Matthew C.; Simmons, Amanda; Park, Hyun Shin; Eyben, Rie von; Kool, Eric T.; Sirjani, Davud; Knox, Sarah M.; Le, Quynh Thu; Mochly‐Rosen, Daria

doi:10.1073/pnas.1802184115

Cited by 24 publications

(30 citation statements)

References 41 publications

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“…A study reported another mechanism that IL-6/STAT3 pathway could be activated through ALDH3A1, contributing to reduced cell proliferation, migration, and invasion in oral squamous cell carcinoma [28], which was in consistent with our findings. However, several studies confirmed that ALDH3A1 was positively associated with tumor cells' progression, which was found in our research [29][30][31][32]. Also, BAG1 highly expressed in gallbladder carcinoma samples was inhibited by microRNA-138, increasing tumor cell proliferation [33].…”

Section: Discussionsupporting

confidence: 80%

ALDH3A1 driving tumor metastasis is mediated by p53/BAG1 in lung adenocarcinoma

Fan¹,

Yin²,

Wang³

et al. 2021

J. Cancer

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Lung adenocarcinoma (LUAD) is a lethal malignancy with metastasis, a major tumor feature that predominantly correlated with progression, but the molecules that mediated tumor metastasis remain elusive. To declare the critical regulatory genes, RNA sequencing data in LUAD patients was acquired from The Cancer Genome Atlas (TCGA) and found that ALDH3A1 was distinctly highly expressed in LUAD patients with metastasis (M1) compared with those without metastasis (M0), linked to the property of cancer stem cell and epithelial-mesenchymal transition (EMT). Besides, high ALDH3A1 expression predicted a poor prognosis. Knockdown of ALDH3A1 showed decreased proliferation, migration, and invasion in A549 cell line. Furthermore, BAG1 was regulated by ALDH3A1 through p53, enhanced cell proliferation, and predicted clinical prognosis. Our findings collectively uncovered a novel mechanism that orchestrates tumor cells' metastasis, and decreasing ALDH3A1 represented a potential therapeutic target for reprogramming metastasis.

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Section: Discussionsupporting

confidence: 80%

ALDH3A1 driving tumor metastasis is mediated by p53/BAG1 in lung adenocarcinoma

Fan¹,

Yin²,

Wang³

et al. 2021

J. Cancer

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“…However, some studies have shown that not all tumors exhibit high levels of ALDH3A1 expression, and the correlation between ALDH3A1 over-expression and estimation of tumor progression or prognosis may not be significant [22,23]. Saiki et al [24] indicated that higher ALDH3A1 protein levels in human head and neck cancer tumors were not associated with worse prognosis. Patel et al [25] reported that ALDH3A1 is expressed at higher levels in normal lung tissues in comparison to small cell lung cancer tissue.…”

Section: Ivyspringmentioning

confidence: 99%

ALDH3A1 acts as a prognostic biomarker and inhibits the epithelial mesenchymal transition of oral squamous cell carcinoma through IL-6/STAT3 signaling pathway

Yang

et al. 2020

J. Cancer

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Objectives: Aldehyde dehydrogenase 3A1 (ALDH3A1) is a member of the ALDH superfamily and its relationship with oral squamous cell carcinoma (OSCC) still unknown. In our subject, we aimed to reveal the expression pattern and clinical value of ALDH3A1 in OSCC and its biological function in OSCC cell lines. Materials and methods: The expression level of ALDH3A1 in paired OSCC tissues and adjacent noncancerous tissues were detected by quantitative real-time PCR, Western blot and immunohistochemistry. The relationship between ALDH3A1 expression and clinical characteristics was analyzed. Besides, cell-counting kit 8, colony formation, wound healing, transwell invasion, apoptosis and cell cycle assays were employed to assess the role of ALDH3A1 in OSCC cells. To explore the influence of ALDH3A1 on OSCC epithelial-to-mesenchymal transition (EMT), the expression of EMT markers (E-cadherin, vimentin, snail, MMP3) on OSCC cells were detected, and possible mechanisms were analyzed. Results: In OSCC tissues, ALDH3A1 was significantly decreased compared to the adjacent normal tissues. Lower ALDH3A1 expression in OSCC tissues was associated with a higher incidence of lymph node metastasis (LNM). Moreover, the overall survival of OSCC with low ALDH3A1 expression was significantly worse compared to that of OSCC with high ALDH3A1 expression. Restored expression of ALDH3A1 suppressed cell proliferation, migration and invasion in OSCC cells. Further experiments showed that ALDH3A1 might inhibit EMT in OSCC via a regulation of the IL-6/STAT3 signal pathway. Conclusion: These data indicate that ALDH3A1 may serve as a biomarker and may be developed into a novel treatment for OSCC.

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“…Changes in the oral microenvironment are related to the radiation dose received by the parotid and submandibular glands 19 – 22 . Limiting the radiation dose to the parotid and submandibular glands can significantly reduce the risk and extent of xerostomia, while also protecting the oral microenvironment 20 , 23 . However, the exact dose limit for these glands is still unclear.…”

Section: Discussionmentioning

confidence: 99%

Oral pH value predicts the incidence of radiotherapy related caries in nasopharyngeal carcinoma patients

Zheng

Meng

et al. 2021

Sci Rep

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Radiotherapy-related caries is a complication of radiotherapy for nasopharyngeal carcinoma; however, factors influencing the occurrence, accurate prediction of onset, and protective factors of radiotherapy-related caries remain unclear. This study analyzed risk factors, disease predictors, and protective factors for radiotherapy-related caries in nasopharyngeal carcinoma. This prospective study included 138 nasopharyngeal carcinoma patients receiving radical radiotherapy at our hospital during June 2012–December 2016 and were followed up for dental caries. Patients’ clinical data on radiotherapy were collected, dynamic monitoring was performed to assess changes in oral pH values, and a questionnaire survey was administered to collect patients’ lifestyle habits. Time-dependent cox regression trees, event-free Kaplan–Meier curve, Mann–Whitely U test were used to analysis the results. The median follow-up time was 30 (12–60) months. Radiotherapy-related caries occurred in 28 cases (20.3%). Univariate analyses showed that radiotherapy-related caries was associated with patient’s age, oral saliva pH value, green tea consumption, and radiation dose to sublingual glands, but not with the radiation dose to the parotid and submandibular glands. Multivariate analysis showed that oral saliva pH value [hazard ratio (HR) = 0.390, 95% confidence interval = 0.204–0.746] was an independent prognostic factor for radiotherapy-related caries. Patients with oral saliva pH values ≤ 5.3 in the 9th month after radiotherapy represented a significantly higher risks for radiotherapy-related caries (p < 0.001). Green tea consumption was associated with the occurrence of radiotherapy-related caries, and oral saliva pH values could predict the occurrence of radiotherapy-related caries. Limiting radiation doses to sublingual glands can reduce the occurrence of radiotherapy-related caries.

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Aldehyde dehydrogenase 3A1 activation prevents radiation-induced xerostomia by protecting salivary stem cells from toxic aldehydes

Cited by 24 publications

References 41 publications

ALDH3A1 driving tumor metastasis is mediated by p53/BAG1 in lung adenocarcinoma

ALDH3A1 driving tumor metastasis is mediated by p53/BAG1 in lung adenocarcinoma

ALDH3A1 acts as a prognostic biomarker and inhibits the epithelial mesenchymal transition of oral squamous cell carcinoma through IL-6/STAT3 signaling pathway

Oral pH value predicts the incidence of radiotherapy related caries in nasopharyngeal carcinoma patients

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