Table 1.
Evidence for V‐ATPase subunit dysregulation in patient tumor tissues
| Cancer type | Subunits investigated | Techniques | Key evidence | References |
|---|---|---|---|---|
| Breast | Voa | RT‐qPCR, IHC | Voa3 mRNA expression was upregulated in all breast cancer tissues tested compared to normal tissue and a3 mRNA expression correlated with tumor grade. Invasive breast cancer tissue had greater a3 staining than ductal carcinoma in situ, suggesting a3 expression increases with invasive potential. | Cotter et al39 |
| Breast and melanoma | Voa2 | IHC, IF | Highly positive staining of Voa2 in breast and skin tumors compared to their respective normal tissues. | Katara et al40 |
| Cervical | V1C1 | IHC | V‐ATPase expression significantly increased in patients with cervical adenocarcinoma. In patients with bulky cervical tumor expression was correlated with poor disease‐free survival | Song et al38 |
| Gastric | V1A | IHC | V1A overexpressed in gastric cancer tissue compared to normal tissue. V1A expression correlated with advanced tumor grade, vascular invasion, lymph node metastasis and was associated with worse survival than patients with negative V1A staining. | Liu et al31 |
| Glioma | Voa | RT‐qPCR | Voa4 isoform increased compared to brain biopsies of epileptic patients. | Gleize et al41 |
| Human hepatocellular carcinoma | Voc (ATP6L) | RT‐qPCR, WB, IHC | Greater ATP6L mRNA and protein expression in HCC tissues compared to normal liver tissue. Baf‐A1 inhibition retarded growth of HCC in liver of mice. | Xu et al19, 42 |
| Lung | V‐ATPase complex | IHC | V‐ATPase complex overexpressed in NSCLC. Expression was significantly lower in grade II adenocarcinoma and squamous cell lung cancer than grade III. V‐ATPase expression was found to be positively correlated to drug resistance in NSCLC samples and a significant positive correlation was obtained for V‐ATPase expression and common cancer chemotherapeutic agents. | Lu et al34 |
| Esophageal | Voa and V1C1 | Confocal microscopy, IHC | V‐ATPase expressed in all stages of neoplastic progression in Barrett's esophagus. | Chueca et al28 |
| V‐ATPase complex | IHC/IF | Complex highly expressed in esophageal squamous cancer cells. | Huang et al29 | |
| V1E1 | IHC | V1E1 expression increased in esophageal cancer tissues than normal esophageal tissue and was directly correlated with tumor invasiveness and poor prognosis. Can act as independent prognostic factor. | Son et al30 | |
| Oral squamous cell carcinoma | V1C1 | RT‐qPCR | V1C1 overexpressed in OSCC tissues compared to healthy oral mucosa samples. | Perez‐Sayans et al36 |
| V1C1 | IHC | V1C1 overexpressed in OSCC tissues compared to healthy oral mucosa tissue. | Garcia‐Garcia et al35 | |
| Ovarian | Voa | IF, IHC | Voa2 expression increased and a3 subunits had greater staining in ovarian cancer tissues compared to normal ovarian tissues. | Kulshrestha et al37 |
| Pancreatic | Voc | RT‐qPCR, IHC, IP | Voc overexpressed in pancreatic carcinoma tissues compared to normal pancreatic tissue. Expression was linked to invasive capabilities as the overexpression of Voc was characteristic of invasive ductal adenocarcinomas. | Ohta et al32 |
| V1E | IHC | V‐ATPase staining was significantly increased from low‐grade pancreatic intraepithelial neoplasia (PanIN) to invasive PDAC. | Chung et al33 |
IHC, Immunohistochemistry; IF, Immunofluorescence; WB, Western blot; IP, Immunoprecipitation.