APPL1 promotes the migration of gastric cancer cells by regulating Akt2 phosphorylation

Liu, Yingxun; Zhang, Chunli; Zhao, Lingyu; Du, Ning; Hou, Ni; Song, Taek Lyul; Huang, Chen

doi:10.3892/ijo.2017.4121

Cited by 6 publications

(5 citation statements)

References 37 publications

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“…APPL1, or DIP13α, is a 709 amino acid endosomal protein that serves as a relay to interact with a range of proteins. 27 Notably, DM mainly results from relative insulin deficiency, which is attributed to impaired signaling or defective insulin secretion. 28 The main peripheral insulin targets, including skeletal muscles, adipose tissues, and the liver, where the APPL1 expression has been determined, indicate the involvement of APPL1 in DM.…”

Section: Discussionmentioning

confidence: 99%

mTOR activation due to APPL1 deficiency exacerbates hyperalgesia via Rab5/Akt and AMPK signaling pathway in streptozocin-induced diabetic rats

Zhang

Zhao

et al. 2019

Mol Pain

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Painful diabetic neuropathy is a common complication of diabetes mellitus with obscure underlying mechanisms. The adaptor protein APPL1 is critical in mediating the insulin sensitizing and insulin signaling. In neurons, APPL1 reportedly affects synaptic plasticity, while its role in the pathogenesis of painful diabetic neuropathy is masked. Our Western blotting revealed significantly decreased APPL1 expression in the dorsal horn in streptozocin-induced rats versus the control rats, coupled with concomitant mechanical and thermal hyperalgesia. Afterward, the determination of exact localization of APPL1 in spinal cord by immunofluorescent staining assay revealed highly expressed APPL1 in the lamina of spinal dorsal horn in control rats, with the overexpression in neurons, microglia, and underexpression in astrocytes. The APPL1 expression in laminae I and II was significantly downregulated in painful diabetic neuropathy rats. In addition, APPL1 deficiency or overexpression contributed to the increase or decrease of Map and Bassoon, respectively. The localization and immunoactivity of APPL1 and mammalian target of rapamycin (mTOR) were determined in spinal dorsal horn in painful diabetic neuropathy rats and control rats by immunohistochemistry, suggesting pronounced decrease in APPL1 expression in the superficial layer of the spinal cord in painful diabetic neuropathy rats, with p-mTOR expression markedly augmented. APPL1 knockdown by infection with lentiviral vector facilitated the activation of mTOR and abrogated mechanical withdrawal threshold values in painful diabetic neuropathy rats. Genetically overexpressed APPL1 significantly eliminated the activation of mTOR and resulted in the augmented mechanical withdrawal threshold values and thermal withdrawal latency values. Furthermore, the APPL1 levels affect phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), and Akt, as well as the small GTPase, Rab5 expression in painful diabetic neuropathy rats. Our results uncovered a novel mechanism by which APPL1 deficiency facilitates the mTOR activation and thus exacerbates the hyperalgesia in streptozocin-induced diabetic rats, presumably via the regulation of Rab5/Akt and AMPK signaling pathway.

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Section: Discussionmentioning

confidence: 99%

mTOR activation due to APPL1 deficiency exacerbates hyperalgesia via Rab5/Akt and AMPK signaling pathway in streptozocin-induced diabetic rats

Zhang

Zhao

et al. 2019

Mol Pain

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“…However, this finding was different from a few studies, which found that APPL1 was highly expressed in cholangiocarcinoma (CHOL), liver hepatocellular carcinoma (LIHC), stomach adenocarcinoma (STAD), and breast cancer. Ding Oxidative Medicine and Cellular Longevity that the expression of APPL1 was upregulated in breast cancer (MCF-7) and liver cancer cells (HepG2), and they verified that APPL1 could promote the proliferation and migration of tumor cells via leptin-mediated phosphorylation of STAT3, ERK1/2, and AKT, which could explain the relevant mechanisms [31][32][33]. The clinical prognosis analysis for KIRC showed that the survival rate was significantly lower in an APPL1-downregulated condition (Figure 3).…”

Section: Discussionmentioning

confidence: 84%

APPL1 Is a Prognostic Biomarker and Correlated with Treg Cell Infiltration via Oxygen-Consuming Metabolism in Renal Clear Cell Carcinoma

Yang

Gong

Song

et al. 2023

Oxidative Medicine and Cellular Longevity

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Kidney renal clear cell carcinoma (KIRC) is one of the most hazardous tumors in the urinary system. The regulation of oxygen consumption in renal clear cell carcinoma is a consequence of adaptive reprogramming of oxidative metabolism in tumor cells. APPL1 is a signaling adaptor involved in cell survival, oxidative stress, inflammation, and energy metabolism. However, the correlation of APPL1 with regulatory T cell (Treg) infiltration and prognostic value in KIRC remain unclear. In this study, we comprehensively predicted the potential function and prognostic value of APPL1 in KIRC. For KIRC patients, relatively low expression of APPL1 was associated with high degree of metastasis, pathological stage, and shorter overall time or poor prognosis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses suggested that low expression of APPL1 may be adapted to the malignant progression of tumors via affecting oxygen-consuming metabolism. In addition, the expression level of APPL1 was negatively correlated with Treg cell infiltration and chemotherapy sensitivity, which indicated that APPL1 may regulate the tumor immune infiltration and chemotherapy resistance by decrease oxygen-consuming metabolic process in KIRC. Therefore, APPL1 may become one of the important prognostic factors, and it may serve as a candidate prognostic biomarker in KIRC.

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“…The majority of other genes identified in the current study have also been reported to be involved in various types of cancer and diseases. These include ABCB7 in myelodysplastic syndromes (31), SFMBT1 in cervical cancer (32), and APPL1 in gastric cancer (33,34). These results may provide helpful evidence for further research into breast cancer.…”

Section: Discussionmentioning

confidence: 90%

Developing a radiosensitivity gene signature for Caucasian patients with breast cancer

Jiang

Jian

et al. 2018

Oncol Rep

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Adjuvant radiotherapy is an important clinical treatment option for patients with breast cancer. However, for Caucasian patients, the clinical benefit of adjuvant radiotherapy can differ from African‑American patients with respect to the overall survival. The goal of the current study was to develop a gene signature and to pre‑identify patients likely to benefit from radiotherapy. Using publicly available breast cancer data from The Cancer Genome Atlas, a new cross‑validation procedure was proposed for developing a gene signature and predicting radiosensitive patients. The results demonstrated that the predicted radiosensitive patients who received radiotherapy exhibited a significantly better survival, while the effect of radiotherapy was not significant for predicted non‑radiosensitive patients. Further hierarchical cluster analysis revealed that the predicted sensitivity for each patient corresponded closely to the results of the cluster analysis. Collectively, the findings of the current study demonstrated that a radiosensitive molecular signature can be used to identify radiosensitive Caucasian patients with breast cancer.

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APPL1 promotes the migration of gastric cancer cells by regulating Akt2 phosphorylation

Cited by 6 publications

References 37 publications

mTOR activation due to APPL1 deficiency exacerbates hyperalgesia via Rab5/Akt and AMPK signaling pathway in streptozocin-induced diabetic rats

mTOR activation due to APPL1 deficiency exacerbates hyperalgesia via Rab5/Akt and AMPK signaling pathway in streptozocin-induced diabetic rats

APPL1 Is a Prognostic Biomarker and Correlated with Treg Cell Infiltration via Oxygen-Consuming Metabolism in Renal Clear Cell Carcinoma

Developing a radiosensitivity gene signature for Caucasian patients with breast cancer

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