Water channel protein AQP1 in cytoplasm is a critical factor in breast cancer local invasion

Abstract

Background Metastasis of breast cancer grows from the local invasion to the distant colonization. Blocking the local invasion step would be promising for breast cancer treatment. Our present study demonstrated AQP1 was a crucial target in breast cancer local invasion. Methods Mass spectrometry combined with bioinformatics analysis was used to identify AQP1 associated proteins ANXA2 and Rab1b. Co-immunoprecipitation, immunofluorescence assays and cell functional experiments were carried out to define the relationship among AQP1, ANXA2 and Rab1b and their re-localization in breast cancer cells. The Cox proportional hazards regression model was performed toward the identification of relevant prognostic factors. Survival curves were plotted by the Kaplan–Meier method and compared by the log-rank test. Results Here, we show that the cytoplasmic water channel protein AQP1, a crucial target in breast cancer local invasion, recruited ANXA2 from the cellular membrane to the Golgi apparatus, promoted Golgi apparatus extension, and induced breast cancer cell migration and invasion. In addition, cytoplasmic AQP1 recruited cytosolic free Rab1b to the Golgi apparatus to form a ternary complex containing AQP1, ANXA2, and Rab1b, which induced cellular secretion of the pro-metastatic proteins ICAM1 and CTSS. Cellular secretion of ICAM1 and CTSS led to the migration and invasion of breast cancer cells. Both in vivo assay and clinical analysis data confirmed above results. Conclusions Our findings suggested a novel mechanism for AQP1-induced breast cancer local invasion. Therefore, targeting AQP1 offers promises in breast cancer treatment.

Characterization of macrophages in head and neck squamous cell carcinoma and development of MRG-based risk signature

“…In this study, AQP1, ITGA5, MAP3K8, PIK3R3, STC1 and TGM2 were significantly overexpressed in HNSCC tumor tissues, while SH2D3C expression was significantly reduced, and there was no difference in ARHGAP4 expression. This is similar to the results of "Guo et al found that AQP1 can promote local invasion of breast cancer, Xu et al found that ITGA5 can promote angiogenesis in cervical cancer, and Lee et al found that MAP3K8 overexpression can induce squamous cell carcinogenesis in the salivary glands of mice" 78 – 80 . Studies have shown that STC1 is not only one of MRGs, but also a glycolysis-related genes in HNSCC, which is prominently expressed in the glycolytic activities of tumor tissues and can also predict the prognosis of HNSCC from the direction of glycolysis, which is similar to the conclusion of this study 81 .…”

SERPINB5 is a prognostic biomarker and promotes proliferation, metastasis and epithelial‐mesenchymal transition (EMT) in lung adenocarcinoma

“…A western blot assay was used to detect SERPINB5 levels after knockdown and levels of EMT markers. Immunohistochemical (IHC) staining was performed as previously described 18 . IHC was used to test for SERPINB5 protein expression levels in paraffin sections.…”

“…Immunohistochemical (IHC) staining was performed as previously described. 18 IHC was used to test for SERPINB5 protein expression levels in paraffin sections.…”

Leptin Promotes Vasculogenic Mimicry in Breast Cancer Cells by Regulating Aquaporin-1

“…AQP1 induces tumor proliferation and metastasis [46]. Breast cancer tumor cells actively utilize water for angiogenesis and AQP1 plays a vital role in water transport by tumor cells [47]. This study revealed for the first time that leptin regulates the expression of AQP1 at both mRNA (Figure 4B) and protein levels (Figure 4C,D).…”