Autophagy plays an important role in stemness mediation and the novel dual function of EIG121 in both autophagy and stemness regulation of endometrial carcinoma JEC cells

Ran, Xiaomin; Zhou, Ping; Zhang, Keqiang

doi:10.3892/ijo.2017.4047

Cited by 31 publications

(26 citation statements)

References 49 publications

(64 reference statements)

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“…Although autophagy may be involved as a tumor suppressor in early phases of cancer development, it seems to be required in advanced tumors. In particular, autophagy was found to be increased in various cancer cell spheres (38,39). Inhibition of autophagy in these models altered CSC behavior.…”

Section: Discussionmentioning

confidence: 95%

Calpain-6 controls the fate of sarcoma stem cells by promoting autophagy and preventing senescence

Andrique¹,

Morardet²,

Linares³

et al. 2018

JCI Insight

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Sarcomas are still unsolved therapeutic challenges. Cancer stem cells are believed to contribute to sarcoma development, but lack of specific markers prevents their characterization and targeting. Here, we show that calpain-6 expression is associated with cancer stem cell features. In mouse models of bone sarcoma, calpain-6-expressing cells have unique tumor-initiating and metastatic capacities. Calpain-6 levels are especially high in tumors that have been successfully propagated in mouse to establish patient-derived xenografts. We found that calpain-6 levels are increased by hypoxia in vitro and calpain-6 is detected within hypoxic areas in tumors. Furthermore, calpain-6 expression depends on the stem cell transcription network that involves Oct4, Nanog, and Sox2 and is activated by hypoxia. Calpain-6 knockdown blocks tumor development in mouse and induces depletion of the cancer stem cell population. Data from transcriptomic analyses reveal that calpain-6 expression in sarcomas inversely correlates with senescence markers. Calpain-6 knockdown suppresses hypoxia-dependent prevention of senescence entry and also promotion of autophagic flux. Together, our results demonstrate that calpain-6 identifies sarcoma cells with stem-like properties and is a mediator of hypoxia to prevent senescence, promote autophagy, and maintain the tumor-initiating cell population. These findings open what we believe is a novel therapeutic avenue for targeting sarcoma stem cells.

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Section: Discussionmentioning

confidence: 95%

Calpain-6 controls the fate of sarcoma stem cells by promoting autophagy and preventing senescence

Andrique¹,

Morardet²,

Linares³

et al. 2018

JCI Insight

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“…It is universally accepted that autophagy actively exists in tumor cells, but there is controversy about the role of autophagy in the progression of tumor [22]. Some researchers believed that autophagy in cancer cells could inhibit the immune reaction, promote tumor growth or induce drug resistance [23][24][25][26]; while others con rmed that autophagy played a role in stimulating tumor antigen cross-presentation, increasing immune cell activation, and improving the survival of patients [15,27,28]. That is to say, the role of autophagy was not always constant, but differed based on the condition.…”

Section: Discussionmentioning

confidence: 99%

The IFN-γ-IDO1-Kynureine Pathway-Induced Autophagy in Cervical Cancer Cell Promotes Phagocytosis of Macrophage

Yang

Tan¹

Niu

et al. 2020

Preprint

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Bachground: Cervical cancer is a common malignant disease in female patients accompanied by active autophagy in tumor cells. However, much remains unknown about the regulatory factors of autophagy and its effect on immune response.Methods: Autophagy in HeLa and SiHa cells treated with IFN-γ, tryptophan depletion, kynurenine, and epacadostat was detected by western blot and autophagy detection kit. After co-cultured with pre-treated HeLa and SiHa cells, U937 was detected by flow cytometry to analyze the CD80, CD86, CD163, CD206 expression and the phagocytosis. Results: IFN-γ could significantly increase the autophagy level of HeLa and SiHa cells by promoting the indoleamine-2,3-dioxygenase-1 (IDO1) expression. HeLa and SiHa cells treated with recombinant human IFN-γ could significantly increase the phagocytosis and CD80, CD86 expression of U937, and this effect was associated with the autophagy in tumor cells. IFN-γ treatment and IDO1 overexpression promote tryptophan depletion and kynurenine accumulation in cervical cancer cells, and the latter was proved to be more potent in inducing autophagy of cervical cancer cells and promoting phagocytosis of macrophage. In vivo, IDO1 overexpression could significantly restrict the tumor growth in C57 mice, and the phagocytosis of macrophage was enhanced.Conclusions: IFN-γ promotes the autophagy of cervical cancer cell possibly through IDO1 expression and kynurenine metabolism, and further promotes macrophage phagocytosis in cervical cancer.

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“…In addition to supporting tumor growth in general, autophagy has been demonstrated to regulate and/or maintain the cancer stem cell phenotype and treatment resistance in multiple studies, for example, in oral squamous cell carcinoma [33] and endometrial cancer [34].…”

Section: Autophagy In Tumorigenesis and Tumor Progressionmentioning

confidence: 99%

Autophagy in Cancer Cell Death

Linder

Kögel

2019

Biology

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Autophagy has important functions in maintaining energy metabolism under conditions of starvation and to alleviate stress by removal of damaged and potentially harmful cellular components. Therefore, autophagy represents a pro-survival stress response in the majority of cases. However, the role of autophagy in cell survival and cell death decisions is highly dependent on its extent, duration, and on the respective cellular context. An alternative pro-death function of autophagy has been consistently observed in different settings, in particular, in developmental cell death of lower organisms and in drug-induced cancer cell death. This cell death is referred to as autophagic cell death (ACD) or autophagy-dependent cell death (ADCD), a type of cellular demise that may act as a backup cell death program in apoptosis-deficient tumors. This pro-death function of autophagy may be exerted either via non-selective bulk autophagy or excessive (lethal) removal of mitochondria via selective mitophagy, opening new avenues for the therapeutic exploitation of autophagy/mitophagy in cancer treatment.

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Autophagy plays an important role in stemness mediation and the novel dual function of EIG121 in both autophagy and stemness regulation of endometrial carcinoma JEC cells

Cited by 31 publications

References 49 publications

Calpain-6 controls the fate of sarcoma stem cells by promoting autophagy and preventing senescence

Calpain-6 controls the fate of sarcoma stem cells by promoting autophagy and preventing senescence

The IFN-γ-IDO1-Kynureine Pathway-Induced Autophagy in Cervical Cancer Cell Promotes Phagocytosis of Macrophage

Autophagy in Cancer Cell Death

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