Grb2 interacts with necrosome components and is involved in rasfonin-induced necroptosis

Hou, Bolin; Huang, Haiwen; Li, Yue-Qian; Liang, Jingnan; Xi, Zhijun; Jiang, Xuejun; Liu, Ling; Li, Erwei

doi:10.1038/s41420-022-01106-1

Cited by 2 publications

(1 citation statement)

References 51 publications

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“…According to gene expression data, the death of treated HCT116 cells occurred through extrinsic apoptosis ( 63 ) mediated by the death receptors DR4 and DR5 encoded by the TNFRSF10A and TNFRSF10B genes, respectively. The overexpression of the GRB2 gene indicated that part of the HCT116 cells was engaged in necrosis/necroptosis ( 64 ), while the overexpression of ULK1 evidenced the occurrence of autophagy ( 65 ) at 24 h after radioisotope addition.…”

Section: Discussionmentioning

confidence: 99%

Modifications in cellular viability, DNA damage and stress responses inflicted in cancer cells by copper-64 ions

Serban,

Niculae,

Manda

et al. 2023

Front. Med.

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Due to combined therapeutical emissions, a high linear energy transfer Auger-electrons with the longer ranged β− particles, 64Cu-based radiopharmaceuticals raise particular theragnostic interest in cancer, by joined therapeutic and real-time PET imaging properties. The in vitro study aimed to investigate the biological and molecular background of 64CuCl2 therapy by analyzing the damages and stress responses inflicted in various human normal and tumor cell lines. Colon (HT29 and HCT116) and prostate carcinoma (DU145) cell lines, as well as human normal BJ fibroblasts, were treated up to 72 h with 2–40 MBq/mL 64CuCl2. Radioisotope uptake and retention were assessed, and cell viability/death, DNA damage, oxidative stress, and the expression of 84 stress genes were investigated at various time points after [64Cu]CuCl2 addition. All the investigated cells incorporated 64Cu ions similarly, independent of their tumoral or normal status, but their fate after exposure to [64Cu]CuCl2 was cell-dependent. The most striking cytotoxic effects of the radioisotope were registered in colon carcinoma HCT116 cells, for which a substantial decrease in the number of metabolically active cells, and an increased DNA damage and oxidative stress were registered. The stress gene expression study highlighted the activation of both death and repair mechanisms in these cells, related to extrinsic apoptosis, necrosis/necroptosis or autophagy, and cell cycle arrest, nucleotide excision repair, antioxidant, and hypoxic responses, respectively. The in vitro study indicated that 40 MBq/mL [64Cu]CuCl2 delivers a therapeutic effect in human colon carcinoma, but its use is limited by harmful, yet lower effects on normal fibroblasts. The exposure of tumor cells to 20 MBq/mL [64Cu]CuCl2, might be used for a softer approach aiming for a lower radiotoxicity in normal fibroblasts as compared to tumor cells. This radioactive concentration was able to induce a persistent decrease in the number of metabolically active cells, accompanied by DNA damage and oxidative stress, associated with significant changes in stress gene expression in HCT116 colon cancer cells.

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Section: Discussionmentioning

confidence: 99%

Modifications in cellular viability, DNA damage and stress responses inflicted in cancer cells by copper-64 ions

Serban,

Niculae,

Manda

et al. 2023

Front. Med.

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mTOR interacts with AIF to positively regulate autophagy

Hou

Gao

Huang

et al. 2023

Preprint

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The mechanism of the positive regulation of autophagy by mammalian target of rapamycin (mTOR) remains largely unknown. In the present study, we observed that inhibition of mTOR either genetically or pharmacologically suppressed basal and H2O2-induced autophagic processes concomitant with marked upregulation of apoptosis inducing factor (AIF) expression. In cells with mTOR knockdown, deprivation of AIF partially rescued both basal and induced autophagy. Importantly, we found that AIF interacted with either mTOR or Beclin1 and that AIF loss markedly enhanced the association of Beclin1 with VPS34, which is essential for autophagy initiation. In contrast, mTOR loss increased the binding of AIF to Beclin1, concomitantly decreasing the interaction between Beclin1 and VPS34. Collectively, the data presented here revealed a previously unnoticed autophagic regulatory pathway in which mTOR functioned as a positive regulator by directly interacting with AIF and autophagic proteins.

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Grb2 interacts with necrosome components and is involved in rasfonin-induced necroptosis

Cited by 2 publications

References 51 publications

Modifications in cellular viability, DNA damage and stress responses inflicted in cancer cells by copper-64 ions

Modifications in cellular viability, DNA damage and stress responses inflicted in cancer cells by copper-64 ions

mTOR interacts with AIF to positively regulate autophagy

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