Rac GTPase activating protein 1 promotes gallbladder cancer via binding DNA ligase 3 to reduce apoptosis

Bian, Rui; Dang, Wei; Song, Xiaoling; Liu, Liguo; Jiang, Chengkai; Yang, Yang; Li, Yongsheng; Li, Lin; Li, Xuechuan; Hu, Yunping; Bao, Runfa; Liu, Yingbin

doi:10.7150/ijbs.58857

Cited by 17 publications

(10 citation statements)

References 46 publications

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“…Elevated RACGAP1 expression has been recorded in various cancers, including hepatocellular carcinoma [ 23 ], basal-like breast cancer [ 24 ], and gallbladder cancer [ 25 ]. RACGAP1 stimulates STAT3 phosphorylation and promotes its nuclear translocation, thus facilitating cell proliferation, migration, and decreased chemosensitivity to doxorubicin in bladder cancer [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

EGF-induced nuclear translocation of SHCBP1 promotes bladder cancer progression through inhibiting RACGAP1-mediated RAC1 inactivation

et al. 2022

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Bladder cancer is a highly heterogeneous and aggressive malignancy with a poor prognosis. EGF/EGFR activation causes the detachment of SHC-binding protein 1 (SHCBP1) from SHC adapter protein 1 (SHC1), which subsequently translocates into the nucleus and promotes cancer development via multiple signaling pathways. However, the role of the EGF-SHCBP1 axis in bladder cancer progression remains unexplored. Herein, we report that SHCBP1 is upregulated in bladder cancer tissues and cells, with cytoplasmic or nuclear localization. Released SHCBP1 responds to EGF stimulation by translocating into the nucleus following Ser273 phosphorylation. Depletion of SHCBP1 reduces EGF-induced cell migration and invasiveness of bladder cancer cells. Mechanistically, SHCBP1 binds to RACGAP1 via its N-terminal domain of amino acids 1 ~ 428, and this interaction is enhanced following EGF treatment. Furthermore, SHCBP1 facilitates cell migration by inhibiting RACGAP-mediated GTP-RAC1 inactivation, whose activity is indispensable for cell movement. Collectively, we demonstrate that the EGF-SHCBP1-RACGAP1-RAC1 axis acts as a novel regulatory mechanism of bladder cancer progression, which offers a new clinical therapeutic strategy to combat bladder cancer.

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Section: Discussionmentioning

confidence: 99%

EGF-induced nuclear translocation of SHCBP1 promotes bladder cancer progression through inhibiting RACGAP1-mediated RAC1 inactivation

et al. 2022

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“…19 The dilution of Trps1 antibody was 1:800. The IHC score was assessed according to previously established criteria [19][20][21][22] and independently evaluated by two experienced pathologists. In summary, the assessment of positive tumor cell proportion involved categorization: 0 represented ≤10% positive cells, 1 indicated ≤50% positive cells, 2 denoted ≤75% positive cells, and 3 signified ≥76% positive cells.…”

Section: Immunohistochemistry and Scoringmentioning

confidence: 99%

Trps1 predicts poor prognosis in advanced high grade serous ovarian carcinoma

Wang,

Sun,

Liu

et al. 2024

Intl Journal of Cancer

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TRPS1 is aberrantly expressed in a variety of tumors, including breast, prostate, and gastric cancers, and is strongly associated with tumorigenesis or prognosis. However, the role of TRPS1 in high grade serous ovarian carcinoma (HGSC) is unknown. We investigated the relationship between TRPS1 expression and clinicopathology in HGSC patients. The tumor‐related regulatory mechanisms of TRPS1 was explored through in vivo and vitro experiments. The results showed that TRPS1 was highly expressed in HGSC compared to normal tissues. It was also linked to the cell proliferation index Ki67 and poor prognosis. In vivo experiments showed that knockdown of TRPS1 could inhibit tumor growth. In vitro experiments, knockdown of TRPS1 inhibited the proliferation of ovarian cancer cells. TRPS1 exerted its regulatory role as a transcription factor, binding to the PSAT1 promoter and promoting the expression of PSAT1 gene. Meanwhile, PSAT1 was positively correlated with CCND1 expression. These results suggest that TRPS1 affects HGSC proliferation and cell cycle by regulating PSAT1 and thus CCND1 expression.

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“…Abnormal expression of Rac GTPase activating protein 1 (RACGAP1) was involved in the pathogenesis and progression of plenty malignant tumors [ 9 , 10 ]. Previous research showed that overexpression of RACGAP1 promoted early HCC recurrence by clinical information collection and preliminary molecular experiment [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Up-Regulation of RACGAP1 Promotes Progressions of Hepatocellular Carcinoma Regulated by GABPA via PI3K/AKT Pathway

Chen

Guo

et al. 2022

Oxidative Medicine and Cellular Longevity

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Hepatocellular carcinoma (HCC) is one of the dominating tumors causing death due to lack of timely discovery and valid treatment. Abnormal increase of Rac GTPase activating protein 1 (RACGAP1) has been verified to be an oncogene in plenty tumors. The profound mechanism of RACGAP1 was rarely reported in HCC. In this study, we explored the function and mechanism of RACGAP1 in HCC through multiple analysis and experiments. RACGAP1 expression was up-regulated in HCC samples and the high expression of RACGAP1 was an independent prognostic risk factor for HCC patients. Meanwhile, RACGAP1 promoted developments of HCC both in vitro and in vivo. We verified that RACGAP1 promoted proliferation of HCC via PI3K/AKT/CDK2 and PI3K/AKT/GSK3β/Cyclin D1 signaling pathway. RACGAP1 accelerated the invasion and metastasis of HCC via phosphorylation of GSK3β and nuclear translocation of β-catenin. Furthermore, by luciferase reporter assay and Chromatin immunoprecipitation (ChIP) assay, we confirmed Recombinant GA Binding Protein Transcription Factor Alpha (GABPA) regulated the transcription of RACGAP1. All these findings revealed that RACGAP1 promotes the progression of HCC through a novel mechanism, which might be a new therapeutic target for HCC patients.

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Rac GTPase activating protein 1 promotes gallbladder cancer via binding DNA ligase 3 to reduce apoptosis

Cited by 17 publications

References 46 publications

EGF-induced nuclear translocation of SHCBP1 promotes bladder cancer progression through inhibiting RACGAP1-mediated RAC1 inactivation

EGF-induced nuclear translocation of SHCBP1 promotes bladder cancer progression through inhibiting RACGAP1-mediated RAC1 inactivation

Trps1 predicts poor prognosis in advanced high grade serous ovarian carcinoma

Up-Regulation of RACGAP1 Promotes Progressions of Hepatocellular Carcinoma Regulated by GABPA via PI3K/AKT Pathway

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