MIIP accelerates epidermal growth factor receptor protein turnover and attenuates proliferation in non-small cell lung cancer

Wen, Jing; Fu, Jianhua; Ling, Yihong; Zhang, Wei

doi:10.18632/oncotarget.7001

Cited by 16 publications

(22 citation statements)

References 39 publications

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“…Further studies on insulin-like growth factor binding protein 2 indicated that MIIP regulates cell migration and mitosis (34). MIIP is underexpressed in a wide range of types of human cancer, including glioma, endometrial cancer, breast cancer, lung cancer, esophageal cancer, prostate cancer, neuroblastoma and pheochromocytoma (3)(4)(5)(6)(7)(8)(9)(10). A decreased MIIP expression is associated with tumorigenesis and progression of endometrial cancer as MIIP inhibits the migration and invasion of endometrial cancer cells (4).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, MIIP inhibits the migration and invasion of glioma cells (6). Wen et al (5) found that MIIP accelerates epidermal growth factor receptor protein turnover and attenuates the proliferation of non-small cell lung cancer cells. Additionally, a previous study conducted by our team indicated that the expression of MIIP mRNA was reduced in human NPC cell lines (5-8F and CNE2) compared with normal nasopharyngeal epithelial cell line (NP69), and the MIIP gene played a notable role in the pathogenesis of NPC (unpublished).…”

Section: Discussionmentioning

confidence: 99%

“…The migration and invasion inhibitory protein (MIIP) gene, also termed IIp45 gene, has a key role in tumorigenesis (3)(4)(5). MIIP gene, which is located in the chromosome 1p36 region and spans 12.6 kb of genomic DNA, inhibits the migration and invasion of cells (3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

“…MIIP gene, which is located in the chromosome 1p36 region and spans 12.6 kb of genomic DNA, inhibits the migration and invasion of cells (3)(4)(5)(6). The chromosome 1p36 region containing MIIP is absent in a wide range of human cancer cases, including NPC (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13), but the role of MIIP in radiosensitivity of NPC has not been studied.…”

Section: Introductionmentioning

confidence: 99%

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MIIP gene expression is associated with radiosensitivity in human nasopharyngeal carcinoma cells

et al. 2018

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Abstract. The present study aims to investigate the radiosensitization effect of the migration and invasion inhibitory protein (MIIP) gene on nasopharyngeal carcinoma (NPC) cells. The MIIP gene was transfected into NPC 5-8F and CNE2 cells. The level of MIIP was analyzed by quantitative reverse transcription-polymerase chain reaction analysis and western blot. The changes in radiosensitivity of the cells were analyzed by colony formation assay. The changes in cell apoptosis and cycle distribution following irradiation were detected by flow cytometry. The expression of BCL2 associated X, apoptosis regulator/B-cell lymphoma 2 was evaluated using western blot. DNA damage was analyzed by counting γ-H2AX foci. The expression levels of γ-H2AX were evaluated by immunofluorescence and western blot. In a previous study by the authors, the results indicated that the expression of MIIP gene evidently increased in MIIP-transfected 5-8F (5-8F OE) and MIIP-transfected CNE2 (CNE2 OE) cells compared with the parental or negative control cells. In the present study, the survival rate of 5-8F OE and CNE2 OE cells markedly decreased following irradiation (0, 2, 4, 6 and 8 Gy) compared with the negative control (5-8F NC and CNE2 NC) and the untreated (5-8F and CNE2) groups. The expression of MIIP was able to increase apoptosis, which resulted in G2/M cell cycle arrest and DNA damage repair was attenuated in 5-8F and CNE2 cells following irradiation as measured by the accumulation of γ-H2AX. It was indicated that MIIP expression is associated with the radiosensitivity of NPC cells and has a significant role in regulating cell radiosensitivity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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MIIP gene expression is associated with radiosensitivity in human nasopharyngeal carcinoma cells

et al. 2018

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“…Decreased acetylation activity of HDAC6 will result to α-tubulin acetylation and reduce cell migration [19]. In addition, MIIP was able to promote EGFR protein degradation and exert a negative effect on lung cancer cells' proliferation [20].…”

Section: Introductionmentioning

confidence: 99%

MIIP downregulates PD-L1 expression through HDAC6 in malignant melanoma

Xing¹,

Li²,

Xiang³

et al. 2020

Preprint

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Background Immune checkpoint inhibitors have improved the objective response rate and survival of melanoma patients. However, there are still many melanoma patients suffering from disease progression due to primary or secondary immune checkpoint inhibitor resistance, as is observed in the failure of anti-PD1/PD-L1 therapy. It is urgent to determine the function of PD-1/PD-L1 expression in melanoma and its associated pathways to enhance the efficacy of anti-PD-1 therapies. Methods A cohort of 133 patients with histologically confirmed melanoma from Tianjin Medical University Cancer Institute & Hospital were included in this study. We performed immunohistochemical staining to detect the expression of MIIP, HDAC6 and PD-L1. Kaplan-Meier and log-rank test were used for survival analyze. As for vitro, Western blot was used to verify the signaling pathway that MIIP regulates PD-L1 expression. Results Our present data demonstrate MIIP expression was decreased in melanoma and that the negative expression of MIIP was correlated with worse overall survival. We also found the positive expression of HDAC6, a molecule that is downstream of MIIP, had a positive trend with decreased overall survival, because the p value was not statistically significant. At the same time, the positive expression of PD-L1, a crucial costimulatory molecule, was associated with decreased overall survival. Furthermore, there was a positive association between HDAC6 and PD-L1 protein expression (p<0.01). In vitro experiment, we found that increasing MIIP led to decreased HDAC6, pSTAT3, and PD-L1 expression. Knocking down MIIP led to increased HDAC6, pSTAT3, and PD-L1 expression. Combining the published results, showing that HDAC6 can regulate PD-L1 expression through STAT3, our present data suggest that MIIP inhibits the expression of PD-L1 by downregulating HDAC6 in melanoma. Most importantly, methods for targeting MIIP-HDAC6-PD-L1 pathways, such as treatment with HDAC6 inhibitors, might indicate a new therapeutic approach for enhancing immune checkpoint inhibitor therapies in melanoma. Conclusions Our findings highlight the immunomodulatory effects of MIIP in the inhibition of PD-L1 expression by downregulating HDAC6 in melanoma. Our data provide a sensible framework to consider the targeting of the MIIP-HDAC6-PD-L1 pathway.

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VNP20009-Abvec-Igκ-MIIP suppresses ovarian cancer progression by modulating Ras/MEK/ERK signaling pathway

Wang,

Tang,

Dai

et al. 2024

Appl Microbiol Biotechnol

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Ovarian cancer poses a significant threat to women’s health, with conventional treatment methods encountering numerous limitations, and the emerging engineered bacterial anti-tumor strategies offer newfound hope for ovarian cancer treatment. In this study, we constructed the VNP20009-Abvec-Igκ-MIIP (VM) engineered strain and conducted initial assessments of its in vitro growth performance and the expression capability of migration/invasion inhibitory protein (MIIP). Subsequently, ID8 ovarian cancer cells and mouse cancer models were conducted to investigate the impact of VM on ovarian cancer. Our results revealed that the VM strain demonstrated superior growth performance, successfully invaded ID8 ovarian cancer cells, and expressed MIIP, consequently suppressing cell proliferation and migration. Moreover, VM specifically targeted tumor sites and expressed MIIP which further reduced the tumor volume of ovarian cancer mice (p < 0.01), via the downregulation of epidermal growth factor receptor (EGFR), Ras, p-MEK, and p-ERK. The downregulation of the PI3K/AKT signaling pathway and the decrease in Bcl-2/Bax levels also indicated VM’s apoptotic potency on ovarian cancer cells. In summary, our research demonstrated that VM exhibits promising anti-tumor effects both in vitro and in vivo, underscoring its potential for clinical treatment of ovarian cancer. Key points • This study has constructed an engineered strain of Salmonella typhimurium capable of expressing anticancer proteins • The engineered bacteria can target and colonize tumor sites in vivo • VM can inhibit the proliferation, migration, and invasion of ovarian cancer cells Graphical Abstract

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MIIP accelerates epidermal growth factor receptor protein turnover and attenuates proliferation in non-small cell lung cancer

Cited by 16 publications

References 39 publications

MIIP gene expression is associated with radiosensitivity in human nasopharyngeal carcinoma cells

MIIP gene expression is associated with radiosensitivity in human nasopharyngeal carcinoma cells

MIIP downregulates PD-L1 expression through HDAC6 in malignant melanoma

VNP20009-Abvec-Igκ-MIIP suppresses ovarian cancer progression by modulating Ras/MEK/ERK signaling pathway

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