The induction of AMPK-dependent autophagy leads to P53 degradation and affects cell growth and migration in kidney cancer cells

Patergnani, Simone; Guzzo, Sonia; Mangolini, Alessandra; Dell’Atti, Lucio; Pinton, Paolo; Aguiari, Gianluca

doi:10.1016/j.yexcr.2020.112190

Cited by 23 publications

(24 citation statements)

References 39 publications

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“…Converse results were observed when MCU was overexpressed. MCU is related to the migration of hepatocellular carcinoma cells [ 17 ], breast cancer cells [ 27 ], colorectal cancer cells [ 18 ], and renal cancer cells [ 28 ]. The epithelial-mesenchymal transition (EMT) process was activated by EMT effectors including vimentin, N-cadherin, and E-cadherin in OSCC [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

MCU That Is Transcriptionally Regulated by Nrf2 Augments Malignant Biological Behaviors in Oral Squamous Cell Carcinoma Cells

Zuo

et al. 2021

BioMed Research International

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Objective. To clarify the role and molecular mechanism of mitochondrial calcium uniporter (MCU) in the malignant biological behaviors of oral squamous cell carcinoma (OSCC) cells through clinical and cellular experiments. Methods. Immunohistochemistry and qRT-PCR techniques were used to observe the expression of MCU, nuclear factor erythroid 2-related factor 2 (Nrf2), mitochondrial calcium uptake 1 (MICU1), and MICU2 in OSCC and normal tissues. After treatment with si-MCU, spermine, and/or sh-Nrf2, malignant biological behaviors of OSCC cells including proliferation, migration, and apoptosis were detected by clone formation, migration, and mitochondrial membrane potential (MMP) assays. Furthermore, MCU, MICU1, MICU2, Nrf2, and other proteins related to malignant biological behaviors were examined using western blot, immunohistochemistry, and immunofluorescence assays. Results. MCU, Nrf2, and MICU1 were strongly expressed in OSCC as compared to normal tissues, while MICU2 was relatively weakly expressed in OSCC tissues. Knockdown of MCU distinctly weakened proliferation and migration and lowered MMP level in CAL 27 cells. Conversely, its activation reinforced migrated capacity and increased MMP level in CAL 27 cells, which was reversed after cotransfection with sh-Nrf2. After treatment with si-MCU or spermine, Nrf2 expression was not affected in CAL 27 cells. However, MCU expression was distinctly suppressed in CAL 27 cells transfected with sh-Nrf2. Furthermore, knockdown of Nrf2 significantly reversed the increase in expression of MICU1 and MICU2 induced by MCU activation in CAL 27 cells. Conclusion. MCU, as a novel oncogene of OSCC, augments malignant biological behaviors of OSCC cells, which could be transcriptionally regulated by Nrf2.

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Section: Discussionmentioning

confidence: 99%

MCU That Is Transcriptionally Regulated by Nrf2 Augments Malignant Biological Behaviors in Oral Squamous Cell Carcinoma Cells

Zuo

et al. 2021

BioMed Research International

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“…Moreover, the p53 R175 degradation by PEITC was reported to be mediated by both the proteasome and autophagy in a concentration-dependent manner, underlying the importance and need for further investigations for the selective degradation mechanism of mutant p53 in order to develop selective autophagy targeting therapeutic strategies. In addition, it is important to note that while the wild type p53 proteins are directed for proteasome-dependent degradation, autophagy-lysosome degradation is also attributed to control cellular p53 stability (169,170). For example, Sunitinib, a small molecule multi kinase inhibitor, approved for the treatment of metastatic renal cell carcinoma, induced autophagic degradation of wild type p53 proteins in multiple cancer cell lines (169).…”

Section: Targeting Mutant P53 By Macroautophagymentioning

confidence: 99%

Mutant p53 as a Regulator and Target of Autophagy

Shi

Norberg

Vakifahmetoglu-Norberg

2021

Front. Oncol.

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One of the most notoriously altered genes in human cancer is the tumor-suppressor TP53, which is mutated with high frequency in more cancers than any other tumor suppressor gene. Beyond the loss of wild-type p53 functions, mutations in the TP53 gene often lead to the expression of full-length proteins with new malignant properties. Among the defined oncogenic functions of mutant p53 is its effect on cell metabolism and autophagy. Due to the importance of autophagy as a stress adaptive response, it is frequently dysfunctional in human cancers. However, the role of p53 is enigmatic in autophagy regulation. While the complex action of the wild-type p53 on autophagy has extensively been described in literature, in this review, we focus on the conceivable role of distinct mutant p53 proteins in regulating different autophagic pathways and further discuss the available evidence suggesting a possible autophagy stimulatory role of mutant p53. Moreover, we describe the involvement of different autophagic pathways in targeting and degrading mutant p53 proteins, exploring the potential strategies of targeting mutant p53 in cancer by autophagy.

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“…TSC1 is an inhibitor of mTORC1 [ 65 ]. Another study demonstrated that overexpression of miR-501-5p increases cell autophagy through activating p-mTOR, leading to p53 degradation in renal cancer, thus facilitating tumor progression of RCC [ 66 ]. Recent research suggests that IMPA2 (inositol monophosphotase 2) leads to decreasing p-mTORC1 levels in ccRCC cells, and thus could be a biomarker for guiding the use of mTOR inhibitors to combat metastatic ccRCC in clinical practice [ 67 ].…”

Section: Mirnas Act As Oncogenes In Renal Cancermentioning

confidence: 99%

A Review of Recent Research on the Role of MicroRNAs in Renal Cancer

Yang

Zou

et al. 2021

Med Sci Monit

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Renal cell carcinoma (RCC) is a most common type of urologic neoplasms; it accounts for 3% of malignant tumors, with high rates of relapse and mortality. The most common types of renal cancer are clear cell carcinoma (ccRCC), papillary renal cell carcinoma (pRCC), and chromophobe renal carcinoma (chRCC), which account for 90%, 6–15%, and 2–5%, respectively, of all renal malignancies. Although surgical resection, chemotherapy, and radiotherapy are the most common treatment method for those diseases, their effects remain dissatisfactory. Furthermore, recent research shows that the treatment efficacy of checkpoint inhibitors in advanced RCC patients is widely variable. Hence, patients urgently need a new molecular biomarker for early diagnosis and evaluating the prognosis of RCC. MicroRNAs (miRNAs) belong to a family of short, non-coding RNAs that are highly conserved, have long half-life evolution, and post-transcriptionally regulate gene expression; they have been predicted to play crucial roles in tumor metastasis, invasion, angiogenesis, proliferation, apoptosis, epithelial-mesenchymal transition, differentiation, metabolism, cancer occurrence, and treatment resistance. Although some previous papers demonstrated that miRNAs play vital roles in renal cancer, such as pathogenesis, diagnosis, and prognosis, the roles of miRNAs in kidney cancer are still unclear. Therefore, we reviewed studies indexed in PubMed from 2017 to 2020, and found several studies suggesting that there are more than 82 miRNAs involved in renal cancers. The present review describes the current status of miRNAs in RCC and their roles in progression, diagnosis, therapy targeting, and prognosis of RCC.

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The induction of AMPK-dependent autophagy leads to P53 degradation and affects cell growth and migration in kidney cancer cells

Cited by 23 publications

References 39 publications

MCU That Is Transcriptionally Regulated by Nrf2 Augments Malignant Biological Behaviors in Oral Squamous Cell Carcinoma Cells

MCU That Is Transcriptionally Regulated by Nrf2 Augments Malignant Biological Behaviors in Oral Squamous Cell Carcinoma Cells

Mutant p53 as a Regulator and Target of Autophagy

A Review of Recent Research on the Role of MicroRNAs in Renal Cancer

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