NPRL2 enhances autophagy and the resistance to Everolimus in castration‐resistant prostate cancer

Chen, Zhixiong; Jiang, Qilong; Zhu, Pingyu; Chen, Yanlin; Xie, Xuemei; Du, Zhongbo; Jiang, Li; Tang, Wei

doi:10.1002/pros.23709

Cited by 46 publications

(37 citation statements)

References 38 publications

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“…Many studies have shown that multiple oncogenes promote PCa cell proliferation, migration, invasion, and inhibiting apoptosis through activating the PI3K-AKT-mTOR signaling pathway [24]. Chen et al found that the high levels of NPRL2 gene expression in prostate cancer cells promote resistance to EVS (an inhibitor of the mTOR) by enhancing autophagy [25]. In addition, TSC1 was significantly associated with DFS in PCa, which is an essential component of the PI3K/ AKT/mTOR signaling pathway [26].…”

Section: Discussionmentioning

confidence: 99%

Development of an autophagy-related gene expression signature for prognosis prediction in prostate cancer patients

Jiang

Luo

et al. 2020

J Transl Med

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Background: Prostate cancer (PCa) is one of the most prevalent cancers that occur in men worldwide. Autophagyrelated genes (ARGs) may play an essential role in multiple biological processes of prostate cancer. However, ARGs expression signature has rarely been used to investigate the association between autophagy and prognosis in PCa. This study aimed to identify and assess prognostic ARGs signature to predict overall survival (OS) and disease-free survival (DFS) in PCa patients. Methods: First, a total of 234 autophagy-related genes were obtained from The Human Autophagy Database. Then, differentially expressed ARGs were identified in prostate cancer patients based on The Cancer Genome Atlas (TCGA) database. The univariate and multivariate Cox regression analysis was performed to screen hub prognostic ARGs for overall survival and disease-free survival, and the prognostic model was constructed. Finally, the correlation between the prognostic model and clinicopathological parameters was further analyzed, including age, T status, N status, and Gleason score. Results: The OS-related prognostic model was constructed based on the five ARGs (FAM215A, FDD, MYC, RHEB, and ATG16L1) and significantly stratified prostate cancer patients into high-and low-risk groups in terms of OS (HR = 6.391, 95% CI = 1.581-25.840, P < 0.001). The area under the receiver operating characteristic curve (AUC) of the prediction model was 0.84. The OS-related prediction model values were higher in T3-4 than in T1-2 (P = 0.008), and higher in Gleason score > 7 than ≤ 7 (P = 0.015). In addition, the DFS-related prognostic model was constructed based on the 22 ARGs (ULK2,

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Section: Discussionmentioning

confidence: 99%

Development of an autophagy-related gene expression signature for prognosis prediction in prostate cancer patients

Jiang

Luo

et al. 2020

J Transl Med

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“…Several studies have revealed that the resistance of cancer cells to a variety of anticancer drugs can increase via upregulation of autophagy [ 118 , 119 ]. Autophagy is a protective mechanism in cancer cells undergoing anticancer therapy.…”

Section: Autophagy As Drug-resistant Factor Of Tumorsmentioning

confidence: 99%

The Roles of Autophagy in Cancer

Yun

Lee

2018

IJMS

770

557

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Autophagy is an intracellular degradative process that occurs under several stressful conditions, including organelle damage, the presence of abnormal proteins, and nutrient deprivation. The mechanism of autophagy initiates the formation of autophagosomes that capture degraded components and then fuse with lysosomes to recycle these components. The modulation of autophagy plays dual roles in tumor suppression and promotion in many cancers. In addition, autophagy regulates the properties of cancer stem-cells by contributing to the maintenance of stemness, the induction of recurrence, and the development of resistance to anticancer reagents. Although some autophagy modulators, such as rapamycin and chloroquine, are used to regulate autophagy in anticancer therapy, since this process also plays roles in both tumor suppression and promotion, the precise mechanism of autophagy in cancer requires further study. In this review, we will summarize the mechanism of autophagy under stressful conditions and its roles in tumor suppression and promotion in cancer and in cancer stem-cells. Furthermore, we discuss how autophagy is a promising potential therapeutic target in cancer treatment.

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“…Similar findings have been demonstrated in a range of other cancers, including estrogen receptor-positive breast cancer where autophagy inhibition can re-sensitise breast cancer cells to tamoxifen [92] . In prostate cancer, high levels of nitrogen permease regulator-like 2, a tumour suppressor candidate gene, can cause resistance to Everolimus by enhancing autophagy via mTOR [93] .…”

Section: Autophagy and Drug Resistancementioning

confidence: 99%

The importance of epithelial-mesenchymal transition and autophagy in cancer drug resistance

Hill¹,

Wang²

2019

CDR

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Epithelial-mesenchymal transition (EMT) and autophagy are both known to play important roles in the development of cancer. Subsequently, these processes are now being utilised as targets for therapy. Cancer is globally one of the leading causes of death, and, despite many advances in treatment options, patients still face many challenges. Drug resistance in cancer-therapy is a large problem, and both EMT and autophagy have been shown to contribute. However, given the context-dependent role of these processes and the complexity of the interactions between them, elucidating how they both act alone and interact is important. In this review, we provide insight into the current landscape of the interactions of autophagy and EMT in the context of malignancy, and how this ultimately may affect drug resistance in cancer therapy.

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NPRL2 enhances autophagy and the resistance to Everolimus in castration‐resistant prostate cancer

Abstract: NPRL2 may act as a pro-growth factor in PCa. The high levels of NPRL2 expression in CRPC promote resistance to EVS by enhancing autophagy. NPRL2 may be a new therapeutic target for intervention of CRPC and a biomarker for predicting resistance to EVS in CRPC.

Cited by 46 publications

References 38 publications

Development of an autophagy-related gene expression signature for prognosis prediction in prostate cancer patients

Development of an autophagy-related gene expression signature for prognosis prediction in prostate cancer patients

The Roles of Autophagy in Cancer

The importance of epithelial-mesenchymal transition and autophagy in cancer drug resistance

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