PTEN/pAkt/p53 signaling pathway correlates with the radioresponse of non-small cell lung cancer

Jung, Il Lae; Kang, Hyo Jin; Kim, Kug Chan; Kim, In Gyu

doi:10.3892/ijmm_00000372

Cited by 21 publications

(4 citation statements)

References 27 publications

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“…Briefly, IR can induce PTEN accumulation to facilitate its therapeutic effects in some tumors. H460 cells obtained enhanced PTEN expression after irradiation in Il Lae Jung's previous research of nonsmall cell lung cancer (67). Similarly, the present radiation dose-dependent increase in PTEN in the IOMM-Lee cells suggests that the abovementioned mechanisms were activated during radiotherapy in meningiomas.…”

Section: Paradoxical Effects Of Ionizing Radiation On Iomm-lee Cellssupporting

confidence: 68%

MicroRNA-221/222 Inhibits the Radiation-Induced Invasiveness and Promotes the Radiosensitivity of Malignant Meningioma Cells

et al. 2020

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The controversy of adjuvant radiotherapy of meningiomas is at least partially due to the insufficient understanding on meningioma cells' response to irradiation and the shortage of radiosensitivity-promotion methods. MicroRNA-221 and microRNA-222 were identified as critical regulators of radiosensitivity in several other tumors. However, their effect in meningiomas has yet to be confirmed. Therefore, the malignant meningioma IOMM-Lee cells were adopted, transfected with microRNA-221/222 mimics or inhibitors, and irradiated with different dosages. The effects of radiation and microRNA-221/222 were then assessed in vitro and in vivo . Radiation dose increases and microRNA-221/222 downregulation synergistically inhibited cell proliferation and colony formation, prevented xenograft tumor progression, and promoted apoptosis, but antagonistically regulated cell invasiveness. Pairwise comparisons revealed that only high-dose radiations (6 and 8 Gy) can significantly promote cell invasiveness in comparison with unirradiated counterparts. Further comparisons exhibited that downregulating the microRNA-221/222 expression can reverse this radiation-induced cell invasiveness to a level of untransfected and unirradiated cells only if cells were irradiated with no more than 6 Gy. In addition, this approach can promote IOMM-Lee's radiosensitivity. Meanwhile, we also detected that the dose rate of irradiation affects cell cycle distribution and cell apoptosis of IOMM-Lee. A high dose rate irradiation induces G0/G1 cell cycle arrest and apoptosis-promoting effect. Therefore, for malignant meningiomas, high-dose irradiation can facilitate cell invasiveness significantly. Downregulating the microRNA-221/222 level can reverse the radiation-induced cell invasiveness while enhancing the apoptosis-promoting and proliferation-inhibiting effects of radiation and promoting cell radiosensitivity.

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Section: Paradoxical Effects Of Ionizing Radiation On Iomm-lee Cellssupporting

confidence: 68%

MicroRNA-221/222 Inhibits the Radiation-Induced Invasiveness and Promotes the Radiosensitivity of Malignant Meningioma Cells

et al. 2020

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“…PTEN activity is lost by mutation, deletion, or promoter methylation silencing at high frequency in many primary and metastatic human cancers 6 . A549 has a higher number of methylated CpG sites in PTEN 28 . Increased PTEN ubiquitination induced by KLHL38 may also be involved.…”

Section: Discussionmentioning

confidence: 97%

KLHL38 involvement in non-small cell lung cancer progression via activation of the Akt signaling pathway

Wang

Jiang

et al. 2021

Cell Death Dis

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Lung cancer is the leading cause of cancer-related death worldwide. KLHL38 has been reported to be upregulated during diapause but downregulated after androgen treatment during the reversal of androgen-dependent skeletal muscle atrophy. This study aimed to clarify the role of KLHL38 in non-small cell lung cancer (NSCLC). KLHL38 expression was evaluated in tumor and adjacent normal tissues from 241 patients with NSCLC using immunohistochemistry and real-time PCR, and its association with clinicopathological parameters was analyzed. KLHL38 levels positively correlated with tumor size, lymph node metastasis, and pathological tumor-node-metastasis stage (all P < 0.001). In NSCLC cell lines, KLHL38 overexpression promoted PTEN ubiquitination, thereby activating Akt signaling. It also promoted cell proliferation, migration, and invasion by upregulating the expression of genes encoding cyclin D1, cyclin B, c-myc, RhoA, and MMP9, while downregulating the expression of p21 and E-cadherin. In vivo experiments in nude mice further confirmed that KLHL38 promotes NSCLC progression through Akt signaling pathway activation. Together, these results indicate that KLHL38 is a valuable candidate prognostic biomarker and potential therapeutic target for NSCLC.

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“…The inhibition of Akt associating with p53 activation and down-regulation of anti-apoptosis have been well recognized [ 36 – 38 , 92 ]. It has been reported that p-Akt restrains the expression of p53 in human lung cancer cells [ 93 ]. Correspondently, the augmentation of p53 level in human lung cancer cells presented in this study might be a consequence of the suppressive activity of norcycloartocarpin on p-Akt/Akt signalling ( Fig 4 ).…”

Section: Discussionmentioning

confidence: 99%

Norcycloartocarpin targets Akt and suppresses Akt-dependent survival and epithelial-mesenchymal transition in lung cancer cells

et al. 2021

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In searching for novel targeted therapeutic agents for lung cancer treatment, norcycloartocarpin from Artocarpus gomezianus was reported in this study to promisingly interacted with Akt and exerted the apoptosis induction and epithelial-to-mesenchymal transition suppression. Selective cytotoxic profile of norcycloartocarpin was evidenced with approximately 2-fold higher IC50 in normal dermal papilla cells (DPCs) compared with human lung cancer A549, H460, H23, and H292 cells. We found that norcycloartocarpin suppressed anchorage-independent growth, cell migration, invasion, filopodia formation, and decreased EMT in a dose-dependent manner at 24 h, which were correlated with reduced protein levels of N-cadherin, Vimentin, Slug, p-FAK, p-Akt, as well as Cdc42. In addition, norcycloartocarpin activated apoptosis caspase cascade associating with restoration of p53, down-regulated Bcl-2 and augmented Bax in A549 and H460 cells. Interestingly, norcycloartocarpin showed potential inhibitory role on protein kinase B (Akt) the up-stream dominant molecule controlling EMT and apoptosis. Computational molecular docking analysis further confirmed that norcycloartocarpin has the best binding affinity of -12.52 kcal/mol with Akt protein at its critical active site. As Akt has recently recognized as an attractive molecular target for therapeutic approaches, these findings support its use as a plant-derived anticancer agent in cancer therapy.

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PTEN/pAkt/p53 signaling pathway correlates with the radioresponse of non-small cell lung cancer

Cited by 21 publications

References 27 publications

MicroRNA-221/222 Inhibits the Radiation-Induced Invasiveness and Promotes the Radiosensitivity of Malignant Meningioma Cells

MicroRNA-221/222 Inhibits the Radiation-Induced Invasiveness and Promotes the Radiosensitivity of Malignant Meningioma Cells

KLHL38 involvement in non-small cell lung cancer progression via activation of the Akt signaling pathway

Norcycloartocarpin targets Akt and suppresses Akt-dependent survival and epithelial-mesenchymal transition in lung cancer cells

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