Combination of cytoplasmic and nuclear girdin expression is an independent prognosis factor of breast cancer

Zhang, Huikun; Yu, Feng; Qin, Fen; Shao, Ying; Chong, Wei; Guo, Zhifang; Liu, Xiaoli; Fu, Li; Gu, Feng; Ma, Yihui

doi:10.1096/fj.201700825rr

Cited by 6 publications

(3 citation statements)

References 46 publications

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“…Immunohistochemical (IHC) staining was performed as described [ 11 ]. In brief, sections (5 μm thick) were dewaxed, hydrated, and heated for antigen retrieval, blocked with hydrogen peroxide and normal goat serum, and subsequently incubated overnight with primary antibody.…”

Section: Methodsmentioning

confidence: 99%

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

Guo

Zhang

Liu

et al. 2023

J Exp Clin Cancer Res

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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.

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Section: Methodsmentioning

confidence: 99%

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

Guo

Zhang

Liu

et al. 2023

J Exp Clin Cancer Res

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“…The CO-IP was performed essentially the same as previously described 43 . Briefly, cellular lysates were obtained in CO-IP lysis buffer and gently rotated at 4 °C overnight followed by centrifuging at 12,000 × g for 10 min.…”

Section: Methodsmentioning

confidence: 99%

Alternative splicing-derived intersectin1-L and intersectin1-S exert opposite function in glioma progression

et al. 2019

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Intersectin1 (ITSN1) contains two isoforms: ITSN1-S and ITSN1-L, which is highly regulated by alternative splicing. However, the alteration of alternative splicing and its importance in cancer is still unknown. In this study, our transcriptome analysis by using a large glioma cohort indicated the two isoforms exerted opposite function in glioma progression. Our previous results had shown ITSN1-S could promote glioma development; however, the function of ITSN1-L remained unknown. In this study, we first confirmed that ITSN1-L exerted an inhibitory role in glioma progression both in vivo and in vitro, which was contrary to the function of ITSN1-S. In additional, we also elucidated the mechanisms of ITSN1-L in inhibiting tumor progression. First, we revealed ITSN1-L could interact with α-tubulin to promote HDAC6-dependent deacetylation of ac-tubulin leading to decreased cell motility. Second, ITSN1-L could attenuate cell–substrate adhesion through FAK/integrin β3 pathway. Third, ITSN1-L was able to strengthen cell–cell adhesion by upregulating N-cadherin expression and its re-localization to membrane by ANXA2 and TUBB3/TUBB4. In conclusion, we found for the first time that two isoforms produced by alternative splicing exerted opposite functions in glioma development. Therefore, upregulation of ITSN1-L expression as well as downregulation of ITSN1-S expression probably was a better strategy in glioma treatment. Our present study laid a foundation for the importance of alternative splicing in glioma progression and raised the possibility of controlling glioma development completely at an alternative splicing level to be a more effective strategy.

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“…The preparation of cytosol/nuclear extract was performed essentially the same as previously described by using the Nuc-Cyto-Mem Preparation Kit (P1201, Applygen Technologies, Beijing, China) [44]. In brief, cells were lysed by Dounce homogenization with prechilled buffer cytosol extraction reagent (CER) on ice.…”

Section: Preparation Of Cytosol/nuclear Extractmentioning

confidence: 99%

Endocytic protein intersectin1-S shuttles into nucleus to suppress the DNA replication in breast cancer

et al. 2021

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Breast cancer is the most common type of cancer worldwide. However, the well-known molecular biomarkers are not enough to meet the needs of precision medicine. In search for novel targets in this regard, we reported ITSN1 (intersectin1) as one of the candidates through mRNA microarray analysis. In the present study, we reported that endocytic protein ITSN1-S exists not only in the cytoplasm but also in nuclei of breast cancer cells. ITSN1-S′ functional nuclear localization signal is within its residues 306–312. Its nuclear export signal (NES) resides within its SH3 domains. We also found, the interaction between the CC domain of nuclear ITSN1-S and the NT domain of nuclear DNA helicase II (NDH II) directly suppressed the DNA replication and nascent DNA synthesis by inhibiting the R-loops resolution in breast cancer cells. Furthermore, the interaction between the EH domains of cytoplasmic ITSN1-S and PI3KC2α inhibit cell migration and invasion by inactivating the PI3KC2α-AKT pathway. Our results were confirmed in both ITSN1 gene knockout cells and in vivo assays. Finally, our clinical data showed a potential application of the combined consideration of the cytoplasmic and nuclear ITSN1-S as an independent prognosis factor. In conclusion, our study revealed ITSN1-S′ novel positioning in the nuclei of breast cancer cells, its function in suppressing DNA replication, and its potential application in improved breast cancer prognosis.

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Combination of cytoplasmic and nuclear girdin expression is an independent prognosis factor of breast cancer

Cited by 6 publications

References 46 publications

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

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

Alternative splicing-derived intersectin1-L and intersectin1-S exert opposite function in glioma progression

Endocytic protein intersectin1-S shuttles into nucleus to suppress the DNA replication in breast cancer

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