Downregulated ATP6V1B1 expression acidifies the intracellular environment of cancer cells leading to resistance to antibody-dependent cellular cytotoxicity

Nishie, Mariko; Suzuki, Eiji; Hattori, Masao; Kawaguch, Kosuke; Kataoka, Tatsuki R.; Hirata, Masahiro; Pu, Fengling; Kotake, Takeshi; Tsuda, Mitsuya; Yamaguchi, Ayane; Sugie, Tomoharu; Toi, Masakazu

doi:10.1007/s00262-020-02732-3

Cited by 16 publications

(10 citation statements)

References 23 publications

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“…It was reported that FAM46A protein was involved in cellular proliferation and associated with nonsmall cell lung cancer (32). Nishie et al revealed the relationship between the expression of ATP6V1B1 and the intracellular environment of cancer cells, suggesting the downregulation of ATP6V1B1 affected the resistance to antibody-dependent cellular cytotoxicity (33). DUOX2, which promoted 5-fluorouracilinduced epithelial-mesenchymal transition by producing reactive oxygen species, appeared to play a significant role in colon cancer chemoresistance and the aggressiveness of this cancer (34).…”

Section: Discussionmentioning

confidence: 99%

Prediction of Biochemical Recurrence-Free Survival of Prostate Cancer Patients Leveraging Multiple Gene Expression Profiles in Tumor Microenvironment

Zhou

Feng

et al. 2021

Front. Oncol.

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Tumor-adjacent normal (TAN) tissues, which constitute tumor microenvironment and are different from healthy tissues, provide critical information at molecular levels that can be used to differentiate aggressive tumors from indolent tumors. In this study, we analyzed 52 TAN samples from the Cancer Genome Atlas (TCGA) prostate cancer patients and developed a 10-gene prognostic model that can accurately predict biochemical recurrence-free survival based on the profiles of these genes in TAN tissues. The predictive ability was validated using TAN samples from an independent cohort. These 10 prognostic genes in tumor microenvironment are different from the prognostic genes detected in tumor tissues, indicating distinct progression-related mechanisms in two tissue types. Bioinformatics analysis showed that the prognostic genes in tumor microenvironment were significantly enriched by p53 signaling pathway, which may represent the crosstalk tunnels between tumor and its microenvironment and pathways involving cell-to-cell contact and paracrine/endocrine signaling. The insight acquired by this study has advanced our knowledge of the potential role of tumor microenvironment in prostate cancer progression.

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Section: Discussionmentioning

confidence: 99%

Prediction of Biochemical Recurrence-Free Survival of Prostate Cancer Patients Leveraging Multiple Gene Expression Profiles in Tumor Microenvironment

Zhou

Feng

et al. 2021

Front. Oncol.

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“…Studies have shown that HEPH has important value in the pathological research and prognostic evaluation of lung cancer [19]. As a multi-subunit enzyme involved in organelle acidi cation, vacuolar ATPase (V-ATPase) cannot be synthesized without ATP6V1B1 [20]. Mariko Nishie et al demonstrated that downregulation of ATP6V1B1 expression acidi es the intracellular environment of breast cancer cells, which in turn leads to resistance to cellular cytotoxicity depended antibody [20].…”

Section: Discussionmentioning

confidence: 99%

“…As a multi-subunit enzyme involved in organelle acidi cation, vacuolar ATPase (V-ATPase) cannot be synthesized without ATP6V1B1 [20]. Mariko Nishie et al demonstrated that downregulation of ATP6V1B1 expression acidi es the intracellular environment of breast cancer cells, which in turn leads to resistance to cellular cytotoxicity depended antibody [20]. The protein encoded by CCNB1 is involved in mitosis.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of Iron Metabolism-Related Genes in Bladder Urothelial Carcinoma

Yue

et al. 2022

Preprint

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Background: Iron metabolism-related genes have shown good predictive value for the prognosis of many solid tumours. However, iron metabolism-related genes have not been reported as prognostic biomarkers in bladder urothelial carcinoma.Methods: In this study, gene expression data and clinical data were downloaded from The Cancer Genome Atlas database. Differential gene expression analysis, univariate Cox regression analysis and the least absolute shrinkage and selection operator regression algorithm were used to screen prognostic iron metabolism-related genes and to construct a risk scoring model. Kaplan-Meier survival plots and receiver operating characteristic curve analysis were used to evaluate the prognostic performance of the risk scoring model in the TCGA-BLCA cohort. In addition, a nomogram model with the risk score was established, and its predictive performance was verified by receiver operating characteristic analysis and calibration plot analysis in the TCGA-BLCA cohort. Gene set enrichment analysis identified pathways and biological processes that may be enriched in the high-risk group. Finally, immune infiltration analysis was used to explore the characteristics of the tumour microenvironment related to the risk score. Results: We identified 14 iron metabolism-related genes with prognostic value and constructed a risk scoring model. Receiver operating characteristic analysis showed that the risk scoring model can accurately predict the 1-year, 3-year, and 5-year overall survival of BLCA patients in the TCGA-BLCA cohort. Kaplan-Meier analysis showed that the overall survival of the high-risk group was significantly lower than that of the low-risk group (P<0.001). The nomogram model effectively predicted the overall survival of BLCA patients in the TCGA-BLCA cohort. Gene set enrichment analysis indicated that iron metabolism-related genes may be involved in biological processes such as developmental processes, the cell cycle, mitosis, the RHO GTPase response, DNA repair, and extracellular matrix regulation. Immune infiltration analysis showed that the level of immune cell infiltration in the high-risk group was high, and the risk score was positively correlated with infiltrating immune cells. Conclusions: Our prognostic model based on iron metabolism-related genes in BLCA could help the prognostic assessment of BLCA patients and provide potential targets for BLCA inhibition.

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“…It has been indicated that the presence of V-ATPase on the surface of tumor cells encourages vesicular trafficking and activation of proteases, which in turn contributes to malignancy (17). New strategies to selectively inhibit V-ATPase are being explored to suppress tumor growth and invasion in various types of solid carcinoma, such as colorectal cancer, breast cancer and renal cell carcinoma (18)(19)(20)(21).…”

Section: High Atp6v1b1 Expression Is Associated With Poor Prognosis A...mentioning

confidence: 99%

High ATP6V1B1 expression is associated with poor prognosis and platinum‑based chemotherapy resistance in epithelial ovarian cancer

et al. 2023

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The vacuolar ATPase H+ transporting V1 subunit B1 (ATP6V1B1) belongs to the family of ATP6Vs, which functions to transport hydrogen ions. The expression of ATP6V1B1 and associated clinicopathological features have been linked to various cancers; however, its role in epithelial ovarian cancer (EOC) has remained to be explored. The present study aimed to unveil the function, molecular mechanisms and clinical significance of ATP6V1B1 in EOC. The mRNA levels of ATP6V1 subunits A, B1 and B2 in EOC tissues were determined using data from the Gene Expression Profiling Interactive Analysis database and RNA sequencing. Protein levels of ATP6V1B1 were evaluated through immunohistochemistry staining of EOC, borderline, benign and normal epithelial tissues. The association between ATP6V1B1 expression and clinicopathological features and prognosis of patients with EOC was analyzed. Furthermore, the biological role of ATP6V1B1 in ovarian cancer cell lines was also assessed. RNA sequencing and public dataset analyses revealed elevated ATP6V1B1 mRNA levels in EOCs. High ATP6V1B1 protein levels were also observed in EOC compared with those of borderline and benign tumors and nonadjacent normal epithelial tissues. High ATP6V1B1 expression was associated with the serous cell type, advanced International Federation of Gynecology and Obstetrics stage, high/advanced tumor grade, elevated serum cancer antigen 125 levels and platinum resistance (P<0.001, P<0.001, P=0.035, P=0.029 and P=0.011, respectively). High expression levels of ATP6V1B1 were also associated with poor overall and disease-free survival (P<0.001). Knockdown of ATP6V1B1 decreased cancer cell proliferation and colony-forming abilities (P<0.001) in vitro by inducing cell cycle arrest in G0/G1 phase. Significant upregulation of ATP6V1B1 was observed in EOC and the prognostic significance and association with chemotherapy resistance of ATP6V1B1 in EOC was demonstrated, rendering it an EOC-related biomarker for prognostic evaluation and chemotherapy resistance, as well as a potential therapeutic target for patients with EOC.

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Downregulated ATP6V1B1 expression acidifies the intracellular environment of cancer cells leading to resistance to antibody-dependent cellular cytotoxicity

Cited by 16 publications

References 23 publications

Prediction of Biochemical Recurrence-Free Survival of Prostate Cancer Patients Leveraging Multiple Gene Expression Profiles in Tumor Microenvironment

Prediction of Biochemical Recurrence-Free Survival of Prostate Cancer Patients Leveraging Multiple Gene Expression Profiles in Tumor Microenvironment

Prognostic Value of Iron Metabolism-Related Genes in Bladder Urothelial Carcinoma

High ATP6V1B1 expression is associated with poor prognosis and platinum‑based chemotherapy resistance in epithelial ovarian cancer

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