IPO7 promotes pancreatic cancer progression via regulating ERBB pathway

Li, Ming; Xu, Dong; Zhan, Yijun; Sheng, T. T.

doi:10.1016/j.clinsp.2022.100044

Cited by 5 publications

(4 citation statements)

References 28 publications

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“…IPO7 belongs to the nucleoplasmic transporter protein family which primarily mediates the nuclear import of proteins [9]. Importantly, IPO7 is upregulated in a variety of cancers, including cervical cancer and pancreatic cancer, with oncogenic functions [12,13]. Herein, we discovered that IPO7 expression was upregulated in OSCC tissues and cells.…”

Section: Discussionmentioning

confidence: 88%

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Importin 7 enhances protective autophagy induced by nuclear translocation of homeobox A10 in oral squamous cell carcinoma

Shanshan Chen,

Jianbo Pan

2024

Cell Mol Biol (Noisy-le-grand)

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Oral squamous cell carcinoma (OSCC) is a common malignant tumor. Importin7 (IPO7) is responsible for nucleoplasmic transport of RNAs and proteins, and it has been confirmed to be involved in the development of human cancers. This study aimed to explore the function and mechanism of IPO7 in OSCC. IPO7 expression in tissues and cells was determined by RT-qPCR. Cell proliferative, migratory, and invasive capabilities were detected through transwell assay and colony formation assay. Mice xenograft models were established for evaluating tumor growth. Autophagy was estimated by the LC3 levels in cells through western blot and immunofluorescence (IF). Western blot was utilized to detect the key proteins in PERK/EIF2AK3/ATF4 pathway for assessing the endoplasmic reticulum stress (ERS). The interaction of IPO7 and homeobox A10 (HOXA10) was tested by GST pull-down assay and Co-IP assay. ChIP assay and luciferase reporter assay were utilized to determine the combination of HOXA10 and EIF2AK3. We proved that IPO7 was upregulated in OSCC tissues and cells, and its depletion reduced cell proliferation, migration, invasion and tumor growth. Furthermore, LC3 expression in cells was found to be reduced by IPO7 knockdown. IPO7 promoted OSCC tumor metastasis by activating autophagy. Additionally, we discovered that IPO7 could regulate ERS by activating the PERK/ATF4 pathway. EIF2AK3 upregulation can promote cell autophagy. Furthermore, IPO7 was proven to promote nuclear translocation of HOXA10 in cells. EIF2AK3 promoter can bind to HOXA10. Rescue assay confirmed that HOXA10 upregulation can reverse the effect of IPO7 silencing on OSCC progression. IPO7 can enhance proliferation, migration, invasion, and autophagy by nuclear translocation of HOXA10 and the activation of EIF2AK3/ATF4 pathway in OSCC.

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Section: Discussionmentioning

confidence: 88%

“…IPO7 overexpression facilitates lung tumorigenesis in mice [11]. IPO7 overexpression remarkably enhanced pancreatic cancer cell proliferation, migration and invasion through modulating the ERBB pathway [12]. IPO7 is correlated with CD8 T cell infiltration and IPO7 overexpression accelerates the development of cervical cancer [13].…”

Section: Introductionmentioning

confidence: 99%

Importin 7 enhances protective autophagy induced by nuclear translocation of homeobox A10 in oral squamous cell carcinoma

Shanshan Chen,

Jianbo Pan

2024

Cell Mol Biol (Noisy-le-grand)

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“…A recent report states that the BOP1 protein is stabilized by long non-coding RNA SNHG6, leading to glycolytic reprogramming in HCC [34]. The IPO7 (importin-7) belongs to the importin-β family and mediates the nuclear import of cargo [35]. In cervical cancer, the IPO7 promoted tumor growth and inversely associated with the in ltration of CD8 + T cells [36].…”

Section: Discussionmentioning

confidence: 99%

Personalized Therapies in Hepatocellular Carcinoma: Insights from a Disulfidptosis-Related Signature

Wan,

Xu,

Zhou

et al. 2024

Preprint

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Hepatocellular carcinoma (HCC) is the predominant pathological type of liver cancer with an unfavorable prognosis. Disulfidptosis is the newest cell death form and plays a vital role in tumorigenesis. However, the role of disulfidptosis-related genes (DRGs) in HCC remains unknown. The RNA-seq and clinical data of HCC patients were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Based on DRGs in TCGA cohort, the predictive model was established via regression analysis of the least absolute shrinkage and selection operator (LASSO) and subsequently validated using ICGC cohort. Moreover, we investigated the relationship between predictive model and clinical features, somatic mutations, molecular mechanism, immune microenvironment and drug response. This study created an eight-gene signature. Here, we noticed a higher level of those eight genes in HCC patients in both RNA and protein levels. The patients in the high-risk group had a poor prognosis. It was found the predictive model was an independent prognostic factor by Multivariate Cox analyses. Pathways involved in cancer, cell membrane, and metabolism was significantly enriched. In addition, tumor mutation burden (TMB) and immune checkpoint genes expression were higher in the high-risk group. Furthermore, the high-risk group was more sensitive to immunotherapy and some targeted therapy. We comprehensively and systematically identified a new disulfidptosis-related signature, which could serve as a valuable tool for predicting prognosis, immune cell infiltration and therapy response of HCC patients. Thus, these discoveries could have potentially clinical value in directing personalized therapies in the future.

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“…There is already evidence that IPO7 and its family of molecules are associated with the acquisition of drug resistance in a variety of cancers [21][22][23]. Disrupting DNA damage repair through the silencing of IPO4 can enhance drug sensitivity [22].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Importin 7-mediated IPO7/c-Myc/IPO7 positive feedback loop suppresses DNA damage repair and improves sorafenib sensitivity in hepatocellular carcinoma

Xue,

Wu,

Zhang

et al. 2023

Preprint

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Background：Hepatocellular carcinoma (HCC) is a common malignancy worldwide with an increasing incidence. Sorafenib is currently the first-line treatment for HCC. However, drug resistance resulting from patients' insensitivity to the medication remains a major cause of high mortality. The specific mechanisms underlying sorafenib resistance in HCC have not yet been fully elucidated. Methods：We have established the function of Importin7 (IPO7) in enhancing sorafenib sensitivity through DNA damage repair pathway through biological information. The expression of IPO7 in hepatocellular carcinoma and normal tissue and cell lines was detected by immunohistochemistry and western blot.Wound healing assay and Transwell assay were employed to examine the function of IPO7. The effect of γ-h2ax on the sensitivity of sorafenib was investigated by down-regulating IPO7. The mechanism between IPO7 and c-Myc was verified by bioinformatics prediction, western blotting, immunoprecipitation (IP), and immunofluorescence assay. Results：Upregulation of IPO7 in liver cancer tissues correlates with an unfavorable prognosis for individuals with liver cancer. The suppression of IPO7 demonstrates a substantial inhibitory effect on the migratory and invasive capabilities of tumor cells. At the same time, inhibition of IPO7 can significantly up-regulate the expression of DNA damage repair factor γH2AX, and improve the sensitivity of sorafenib. Additionally, our findings demonstrate that IPO7 promotes the nuclear translocation of c-Myc, leading to the activation of the IPO7-driven DNA damage repair response to sorafenib. Conclusion: Our results provide new insights into the sensitivity of IPO7 to sorafenib and provide new potential targets for further investigation.

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IPO7 promotes pancreatic cancer progression via regulating ERBB pathway

Cited by 5 publications

References 28 publications

Importin 7 enhances protective autophagy induced by nuclear translocation of homeobox A10 in oral squamous cell carcinoma

Importin 7 enhances protective autophagy induced by nuclear translocation of homeobox A10 in oral squamous cell carcinoma

Personalized Therapies in Hepatocellular Carcinoma: Insights from a Disulfidptosis-Related Signature

Inhibition of Importin 7-mediated IPO7/c-Myc/IPO7 positive feedback loop suppresses DNA damage repair and improves sorafenib sensitivity in hepatocellular carcinoma

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