RAC1 Involves in the Radioresistance by Mediating Epithelial-Mesenchymal Transition in Lung Cancer

Tan, Shiming; Yi, Pin; Wang, Heran; Xia, Longzheng; Han, Yaqian; Wang, Hui; Zeng, Biao; Tang, Lu; Pan, Qing; Tian, Yutong; Rao, Shan; Oyang, Linda; Liang, Jiaxin; Lin, Jinguan; Su, Min; Shi, Ying; Liao, Qianjin; Zhou, Yujuan

doi:10.3389/fonc.2020.00649

Cited by 22 publications

(19 citation statements)

References 56 publications

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“…RP-4, a new type of radiosensitizer derived from rhein, activates the sensitivity of nasopharyngeal carcinoma (NPC) cells to radiotherapy by targeting the Rac1-NADPH pathway (149). Our research team has confirmed that Rac1 can target the PAK1-LIMK1-Cofilins signaling pathway to cause radiotherapy resistance in lung cancer (150). In the treatment of head and neck squamous cell carcinoma (HNSCC), it was found that the combination of Rac1 inhibitors based on radiotherapy can improve the therapeutic effect (151).…”

Section: Rac1 Is Involved In the Regulation Of Resistance To Tumor Therapymentioning

confidence: 79%

Rac1, A Potential Target for Tumor Therapy

et al. 2021

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RAS-related C3 botulinum toxin substrate 1 (Rac.1) is one of the important members of Rho GTPases. It is well known that Rac1 is a cytoskeleton regulation protein that regulates cell adhesion, morphology, and movement. Rac1 is highly expressed in different types of tumors, which is related to poor prognosis. Studies have shown that Rac1 not only participates in the tumor cell cycle, apoptosis, proliferation, invasion, migration and angiogenesis, but also participates in the regulation of tumor stem cell, thus promoting the occurrence of tumors. Rac1 also plays a key role in anti-tumor therapy and participates in immune escape mediated by the tumor microenvironment. In addition, the good prospects of Rac1 inhibitors in cancer prevention and treatment are exciting. Therefore, Rac1 is considered as a potential target for the prevention and treatment of cancer. The necessity and importance of Rac1 are obvious, but it still needs further study.

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Section: Rac1 Is Involved In the Regulation Of Resistance To Tumor Therapymentioning

confidence: 79%

Rac1, A Potential Target for Tumor Therapy

et al. 2021

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“…The RAC1 was critical for cellular adhesion, migration, motility and cell proliferation [51]. PI3K/AKT signaling pathway induced RAC1 expression and activity, and then enhanced cell proliferation, survival, migration and metastasis [52].…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology and Experiment Verification to Explore the Potential Mechanism of Yin-Huo-Tang for Lung Adenocarcinoma Recurrence

Liu

Lin

et al. 2021

Preprint

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BackgroundLung adenocarcinoma (LUAD) is one of the most common malignancies with a rise in new cases worldwide each year. Recurrence significantly influences the survival in patients with LUAD. Yin-Huo-Tang (YHT) is a classic traditional Chinese prescription, used to prevent lung cancer relapse by “nourishing yin and clearing heat”. MethodsIn this study, the mechanism of YHT in LUAD recurrence was investigated. Firstly, the bioactive compounds-targets network and the protein–protein interaction network were constructed, and functional annotation and pathway enrichment analyses were performed. Pivotal compounds and hub genes were selected from the networks. Subsequently, the effectiveness of YHT was confirmed in lewis lung carcinoma mice. RNA sequencing was used to explore the mRNA expression differences between tumor tissues in the model mouses and YHT-treated mouses. The pathways screened by network pharmacology and RNA sequencing analysis at the same time were considered the most important pathways. At last, qualitative phytochemical analysis, molecular docking technology, PCR and WB analysis were used to validate the pivotal active ingredients, hub genes and main pathways.ResultsThere were 128 active compounds, 419 targets interacting with LUAD recurrence. Network analysis identified 4 pivotal compounds, 28 hub genes and 30 main pathways. Target genes mainly focused on inflammation, metabolism, immune responses and apoptosis. We confirmed that YHT could inhibit the recurrence of lung adenocarcinoma through animal experimental study. Sphingolipid signaling pathway was the common main pathway in network pharmacology and RNA sequencing results. The hub genes related with the sphingolipid signaling pathway was S1PR5. Qualitative phytochemical analysis of the water extract of YHT confirmed the presence of 3 pivotal compounds, namely stigmasterol, nootkatone and ergotamine. The results of molecular docking verified the pivotal compounds of YHT could good affinity with the S1PR5. The PCR and WB analysis verified YHT suppressed lewis lung cancer cells proliferation by inhibiting S1P/S1PR5/Gi/Ras/Raf/MEK/ERK pathway, and inhibited migration through S1P/S1PR5/Gi/PI3K/RAC pathway.ConclusionThe results confirmed the therapeutic effect of YHT on the recurrence of LUAD by multi-component-multi-target mode, the sphingolipid signaling pathway was one of the most relevant potential signaling pathways.

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“…The plating efficiency (PE) was calculated as the number of colonies/planted cells×100%, and the survival fraction (SF) was calculated as the irradiated colony formation rate/unirradiated colony formation rate×100%. The single-hit multitarget model was used to fit the cell survival curve, and the mean lethal dose (D0), the quasi-threshold dose (Dq), and the sensitizing enhancement ratio (SER) values were calculated with Prism 8 statistical software [ 16 ].…”

Section: Methodsmentioning

confidence: 99%

Overexpression of Notch2 enhances radiosensitivity via inhibition of the AKT/mTOR signaling pathway in nasopharyngeal carcinoma

Huang

et al. 2021

Bioengineered

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Our previous study found that in nasopharyngeal carcinoma (NPC) cells, overexpression of Notch2 can inhibit epithelial-mesenchymal transition (EMT), which plays a vital role in mediating radiosensitivity. The purpose of this study was to explore the radiosensitizing efficacy of the Notch2 gene in NPC cells and its potential mechanism. We used the recombinant plasmid transfection technique to establish Notch2-overexpressing 5-8 F and CNE-2 NPC cells. Cell proliferation, radiosensitivity, apoptosis and cell cycle distribution were assessed by cell counting kit-8 (CCK-8) experiments, colony formation experiments and flow cytometry. The levels of proteins related to cell cycle, apoptosis, and the AKT/mTOR signaling pathway were evaluated by using Western blotting. The results suggested that Notch2 overexpression increased the radiosensitivity of NPC cells, with sensitizing enhancement ratios (SERs) of 1.24 (5-8 F cells) and 1.34 (CNE-2 cells). Flow cytometry indicated that the level of apoptosis and percentage of cells in G2/M-phase were highest in NPC cells overexpressing Notch2 and treated with radiotherapy compared to cells overexpressing Notch2 alone or administered radiotherapy alone. Western blotting showed that compared to that of cells treated with Notch2 overexpression or radiotherapy alone, the levels of γH2AX, Bax, Bcl-2, Cyclin D1 and AKT/mTOR signaling pathway-related proteins were modified in NPC cells overexpressing Notch2 and treated with radiotherapy. These findings showed that overexpression of Notch2 can increase the radiosensitivity of NPC cells by inhibiting the AKT/ mTOR pathway.

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RAC1 Involves in the Radioresistance by Mediating Epithelial-Mesenchymal Transition in Lung Cancer

Cited by 22 publications

References 56 publications

Rac1, A Potential Target for Tumor Therapy

Rac1, A Potential Target for Tumor Therapy

Network Pharmacology and Experiment Verification to Explore the Potential Mechanism of Yin-Huo-Tang for Lung Adenocarcinoma Recurrence

Overexpression of Notch2 enhances radiosensitivity via inhibition of the AKT/mTOR signaling pathway in nasopharyngeal carcinoma

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