Cullin7 enhances resistance to trastuzumab therapy in Her2 positive breast cancer via degrading IRS-1 and downregulating IGFBP-3 to activate the PI3K/AKT pathway

Qiu, Ni; He, Yuhang; Zhang, Siming; Zhan, Yongtao; Han, Guodong; Jiang, Ming; He, Weixing; Zhou, Jie; Liang, Haibin; Ao, Xiang; Xia, Haoming; Li, Jia; Yang, Yuyang; He, Zhiwei; Zou, Zhengzhi; Li, Hongsheng

doi:10.1016/j.canlet.2019.08.008

Cited by 28 publications

(19 citation statements)

References 51 publications

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“…The PI3K/AKT signaling pathway has been demonstrated to serve important roles in various pathophysiologic processes, including tumor growth, apoptosis, migration and invasiveness, as well as in EMT (31,32). Certainly, the PI3K/AKT signaling pathway serves a central role in the progression of BC (33). It has previously been reported that the activation of ELF3 may inhibit the PI3K/AKT signaling pathway in lung cancer regulated by miR-320 (14,29).…”

Section: Discussionmentioning

confidence: 99%

miR‑320/ELF3 axis inhibits the progression of breast cancer via the PI3K/AKT pathway

Zhang

Geng

et al. 2020

Oncol Lett

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There is increasing evidence demonstrating that disorders affecting microRNAs (miRs) influence tumorigenesis and progression, which results in a poor prognosis in patients with breast cancer (BC). In the present study, the precise molecular mechanism underlying the role of miR-320 in the progression of BC was investigated. Reverse transcription-quantitative PCR was conducted to determine mRNA expression, and western blot analysis was used to test protein levels. An MTT assay was conducted to detect cell viability and Transwell assays were used to analyze cell migration and invasion abilities. Furthermore, E74-like factor 3 (ELF3) protein density was tested via immunohistochemistry. Tumor volume was detected by xenograft tumor formation assay. The current results indicated that miR-320 expression was downregulated in BC tissues and cells, and was associated with a poor prognosis of patients with BC. Overexpression of miR-320 inhibited cell proliferation, migration and invasion via inhibition of the epithelial-mesenchymal transition and the PI3K/AKT signaling pathway in BC cells. Furthermore, it was revealed that the tumor size and weight were smaller in nude mice that had been transfected to overexpress miR-320. The luciferase reporter assay demonstrated the direct binding of miR-320 to the 3' untranslated region of ELF3 mRNA, which may further downregulate ELF3. Overall, the present results provided evidence that miR-320 may be a tumor suppressor in BC, and that the miR-320/ELF3 axis regulated tumor progression via the PI3K/AKT signaling pathway, which may represent a novel treatment strategy for BC.

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Section: Discussionmentioning

confidence: 99%

miR‑320/ELF3 axis inhibits the progression of breast cancer via the PI3K/AKT pathway

Zhang

Geng

et al. 2020

Oncol Lett

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“…Despite the significant progress that has been made in the development of anti-tumor drugs for breast cancer over the past few decades, especially in targeted therapy, 2,3,5 the majority of cancer patients may relapse and suffer from serious side effects caused by these innovative treatments. [6][7][8] In recent years, immunotherapy, particularly for adoptive CIK cell transfer, has become an important neoadjuvant therapeutic approach for breast cancer treatment. [9][10][11]14 To further improve the significant promise of adoptively transferred CIK cells immunotherapy, a noninvasive and tomographic method is required to visualize and monitor these transferred cells invivo.…”

Section: Discussionmentioning

confidence: 99%

“…4,5 However, to further improve the efficiency of breast cancer treatment is a new challenge due to the development of treatment resistance and side effects. [6][7][8] Currently, immunotherapy is considered as a promising treatment option for cancer, 9 and adoptive cytokine-induced killer (CIK) cell transfer is commonly used in a variety of tumor immunotherapeutic strategies due to its advantage. [10][11][12][13][14] CIK cells are induced by culturing peripheral blood mononuclear cells (PBMCs) with the addition of an anti-CD3 antibody, recombinant human interleukin (rhIL-1α), recombinant human interferon gamma (rhIFN-γ) and recombinant human interleukin-2 (rhIL-2), and mainly consist of a CD3 + T cell population which simultaneously express a natural killer cell marker CD56.…”

Section: Introductionmentioning

confidence: 99%

<p><sup>18</sup>F-FHBG PET-CT Reporter Gene Imaging of Adoptive CIK Cell Transfer Immunotherapy for Breast Cancer in a Mouse Model</p>

Yin

et al. 2020

OTT

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“…[6][7][8] . Among these, the phosphate idylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway was found to play a central role in the cell physiology of breast cancer [9][10][11] . Mutations in the PI3K/AKT/ mTOR pathway are frequently detected in breast cancer.…”

Section: Introductionmentioning

confidence: 99%

A novel 4-aminoquinazoline derivative, DHW-208, suppresses the growth of human breast cancer cells by targeting the PI3K/AKT/mTOR pathway

et al. 2020

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Breast cancer is one of the most frequent cancers among women worldwide. However, there is still no effective therapeutic strategy for advanced breast cancer that has metastasized. Aberrant activation of the PI3K/AKT/mTOR pathway is an essential step for the growth of human breast cancers. In our previous study, we designed and synthesized DHW-208 (2,4-difluoro-N-(5-(4-((1-(2-hydroxyethyl)-1H-pyrazol-4-yl)amino)quinazolin-6-yl)-2methoxypyridin-3-yl)benzenesulfonamide) as a novel pan-PI3K inhibitor. This study aimed to assess the therapeutic efficacy of DHW-208 in breast cancer and investigate its underlying mechanism. We found that DHW-208 inhibited the growth, proliferation, migration, and invasion of breast cancer cells. Moreover, DHW-208 induced breast cancer cell apoptosis via the mitochondrial pathway and induced G0/G1 cell-cycle arrest. In vitro results show that DHW-208 is a dual inhibitor of PI3K and mTOR, and suppress the growth of human breast cancer cells by targeting the PI3K/AKT/ mTOR pathway. Consistent with the in vitro results, in vivo studies demonstrated that DHW-208 elicits an antitumor effect by inhibiting the PI3K/AKT/mTOR-signaling pathway with a high degree of safety in breast cancer. Above all, we report for the first time that DHW-208 suppressed the growth of human breast cancer cells by inhibiting the PI3K/AKT/ mTOR-signaling pathway both in vivo and in vitro. Our study may provide evidence for the use of DHW-208 as an effective, novel therapeutic candidate for the treatment of human breast cancers in clinical trials.

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Cullin7 enhances resistance to trastuzumab therapy in Her2 positive breast cancer via degrading IRS-1 and downregulating IGFBP-3 to activate the PI3K/AKT pathway

Cited by 28 publications

References 51 publications

miR‑320/ELF3 axis inhibits the progression of breast cancer via the PI3K/AKT pathway

miR‑320/ELF3 axis inhibits the progression of breast cancer via the PI3K/AKT pathway

<p><sup>18</sup>F-FHBG PET-CT Reporter Gene Imaging of Adoptive CIK Cell Transfer Immunotherapy for Breast Cancer in a Mouse Model</p>

A novel 4-aminoquinazoline derivative, DHW-208, suppresses the growth of human breast cancer cells by targeting the PI3K/AKT/mTOR pathway

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