Ubiquitin‑specific peptidase 17 promotes cisplatin resistance via PI3K/AKT activation in non‑small cell lung cancer

Zhang, Shengchao; Xu, Zicheng; Yuan, Jun; Chen, Hao

doi:10.3892/ol.2020.11568

Cited by 5 publications

(4 citation statements)

References 44 publications

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“…The PI3K/AKT pathway is related to the development and progression of a range of cancers [ 38 – 40 ]. Zhang et al [ 41 ] discovered that PI3K/AKT is involved in cisplatin resistance in NSCLC. Zhang et al [ 42 ] showed that PI3K/Akt signaling pathway inhibition enhanced AZD9291-induced cell death.…”

Section: Discussionmentioning

confidence: 99%

Hypoxic Microenvironment-Induced Reduction in PTEN-L Secretion Promotes Non-Small Cell Lung Cancer Metastasis through PI3K/AKT Pathway

Song

Shi

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. Lung cancer is the leading cause of cancer-related deaths worldwide. The aim of this study was to investigate the effects of hypoxic microenvironment on PTEN-L secretion and the effects of PTEN-L on the metastasis of non-small cell lung cancer (NSCLC) and the potential mechanisms. Methods. The expression levels of PTEN-L in NSCLC tissues, cells, and cell culture media were detected. The transfection of PTEN-L overexpression construct or HIF-1α-siRNAs was conducted to manipulate the expression of PTEN-L or HIF-1α. NSCLC cells were introduced into 200 μM CoCl2 medium for 72 hours under 37°C to simulate hypoxia. The proliferation and apoptosis of the A549 cells were determined by the Cell Counting Kit-8 assay and Annexin V-FITC/PI-stained flow cytometry assay, respectively. Wound healing assay and transwell invasion assay were used to measure the migration and invasion of A549 cells. The protein expression of PTEN, PTEN-L, PI3K/AKT pathway-related proteins, and HIF-1α was detected by Western blot. Results. PTEN and PTEN-L are downregulated in lung cancer tissues and cells. The protein expression of PTEN-L in the culture medium of lung cancer cell lines is decreased. The hypoxic microenvironment inhibits PTEN-L secretion. The low level of PTEN-L promotes cell proliferation, migration, and invasion, as well as inhibits apoptosis of A549 cells. The overexpression of PTEN-L attenuated the activation of the PI3K/AKT pathway by the hypoxic microenvironment. The knockdown of HIF-1α upregulates PTEN-L secretion under hypoxia. Conclusions. The hypoxic microenvironment inhibits PTEN-L secretion and thus activates PI3K/AKT pathway to induce proliferation, migration, and invasion promotion, and apoptosis inhibition in NSCLC cells.

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Section: Discussionmentioning

confidence: 99%

Hypoxic Microenvironment-Induced Reduction in PTEN-L Secretion Promotes Non-Small Cell Lung Cancer Metastasis through PI3K/AKT Pathway

Song

Shi

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…USP17 subfamily genes encoding deubiquitinating enzymes were identified as immediate early genes that can be rapidly induced in response to cytokine stimulation in mice and humans [ 31 ]. Specifically, USP17 has been shown to regulate inflammation, cell motility, Th17 cell development, and oncogenesis [ 32 ]. Moreover, high levels of USP17 have been shown to promote G1-S transition and cell proliferation in multiple cancer cell types.…”

Section: Discussionmentioning

confidence: 99%

A Case Series Exploration of Multi-Regional Expression Heterogeneity in Triple-Negative Breast Cancer Patients

Kaur

Wylie

et al. 2022

IJMS

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Extensive intratumoral heterogeneity (ITH) is believed to contribute to therapeutic failure and tumor recurrence, as treatment-resistant cell clones can survive and expand. However, little is known about ITH in triple-negative breast cancer (TNBC) because of the limited number of single-cell sequencing studies on TNBC. In this study, we explored ITH in TNBC by evaluating gene expression-derived and imaging-derived multi-region differences within the same tumor. We obtained tissue specimens from 10 TNBC patients and conducted RNA sequencing analysis of 2–4 regions per tumor. We developed a novel analysis framework to dissect and characterize different types of variability: between-patients (inter-tumoral heterogeneity), between-patients across regions (inter-tumoral and region heterogeneity), and within-patient, between-regions (regional intratumoral heterogeneity). We performed a Bayesian changepoint analysis to assess and classify regional variability as low (convergent) versus high (divergent) within each patient feature (TNBC and PAM50 subtypes, immune, stroma, tumor counts and tumor infiltrating lymphocytes). Gene expression signatures were categorized into three types of variability: between-patients (108 genes), between-patients across regions (183 genes), and within-patients, between-regions (778 genes). Based on the between-patient gene signature, we identified two distinct patient clusters that differed in menopausal status. Significant intratumoral divergence was observed for PAM50 classification, tumor cell counts, and tumor-infiltrating T cell abundance. Other features examined showed a representation of both divergent and convergent results. Lymph node stage was significantly associated with divergent tumors. Our results show extensive intertumoral heterogeneity and regional ITH in gene expression and image-derived features in TNBC. Our findings also raise concerns regarding gene expression based TNBC subtyping. Future studies are warranted to elucidate the role of regional heterogeneity in TNBC as a driver of treatment resistance.

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“…It has been reported that CDDP increased the levels of USP17 expression. USP17 also induced the NSCLC cell proliferation through PI3K/AKT activation [44]. HSPA12B belongs to the HSP70 protein family that is directly associated with CDDP resistance through p-IκBα and p-AKT upregulations and caspase-3 downregulation in lung tumor cells [45].…”

Section: Lung Cancermentioning

confidence: 99%

PI3K/AKT signaling pathway as a critical regulator of Cisplatin response in tumor cells

Navaei¹,

Khalili-Tanha²,

Zangouei³

et al. 2021

Oncology Research

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Chemotherapy is one of the main therapeutic modalities for cancer patients. Cisplatin (CDDP), as one of the first-line drugs, is of great importance in the chemotherapy of various tumors. However, a significant percentage of cancer patients are resistant to CDDP treatment. Due to the CDDP side effects on normal tissues, the diagnosis of CDDP resistance is required to suggest the most efficient therapeutic strategies for cancer patients. Several molecular mechanisms and signaling pathways are associated with CDDP response. The PI3K/AKT signaling pathway has a pivotal role in the transmission of extracellular signals into the cells to regulate various pathophysiological processes such as cell proliferation, migration, and drug resistance. In the present review, we summarized all of the studies which have been reported on the role of PI3K/AKT pathway in regulation of CDDP response. It was shown that the PI3K/AKT pathway is mainly involved in CDDP response in lung, ovarian, and gastrointestinal cancers. It was also observed that the non-coding RNAs have a key role in CDDP response by regulation of PI3K/AKT pathway. This review paves the way for suggesting a PI3K/AKT-related panel marker for the prediction of CDDP response in different cancer patients.

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Ubiquitin‑specific peptidase 17 promotes cisplatin resistance via PI3K/AKT activation in non‑small cell lung cancer

Cited by 5 publications

References 44 publications

Hypoxic Microenvironment-Induced Reduction in PTEN-L Secretion Promotes Non-Small Cell Lung Cancer Metastasis through PI3K/AKT Pathway

Hypoxic Microenvironment-Induced Reduction in PTEN-L Secretion Promotes Non-Small Cell Lung Cancer Metastasis through PI3K/AKT Pathway

A Case Series Exploration of Multi-Regional Expression Heterogeneity in Triple-Negative Breast Cancer Patients

PI3K/AKT signaling pathway as a critical regulator of Cisplatin response in tumor cells

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