Heat Shock Factor 1 (HSF1) Controls Chemoresistance and Autophagy through Transcriptional Regulation of Autophagy-related Protein 7 (ATG7)

Desai, Shruti; Liu, Zixing; Yao, Jun; Patel, Nishant; Chen, Jieqing; Wu, Yun; Ahn, Eun-Young; Fodstad, Øystein; Tan, Ming

doi:10.1074/jbc.m112.422071

Cited by 124 publications

(91 citation statements)

References 44 publications

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“…In mouse embryonic fibroblasts, panobinostat-induced formation of autophagic vesicles was prevented by HSP70 knockout, 92 whereas, in human breast adenocarcinoma cells, exposure to the chemotherapeutic agent carboplatin increased autophagy as indicated by an increase in LC3 punctate structures and LC3 and ATG7 protein expression that was prevented by knockdown of HSF1. 93 It was also reported that silencing of TPR (translocated promoter region, nuclear basket protein) a component of the nuclear pore complex leading to a significant reduction in nuclear pore numbers results in a significant increase in autophagy that is associated with an increase in heat stress response in HeLa cells (see a comprehensive diagram illustrating the intracellular mechanisms regulating autophagy in translocated promoter region, nuclear basket protein-depleted cells). 94 In mouse with progression of Alzheimer-like deficits, the autophagy-activating agent rapamycin (an inhibitor of MTOR) results in HSF1 activation and HSPs overexpression in the brain.…”

Section: A Correspondence Between Immune and Muscle Cellsmentioning

confidence: 99%

Heat shock response and autophagy—cooperation and control

2015

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Abbreviations: AKT, v-akt murine thymoma viral oncogene homolog 1; AMPK, adenosine monophosphate-activated protein kinase; ATG, autophagy-related; BECN1, Beclin 1, autophagy related; EIF4EBP1, eukaryotic translation initiation factor 4E binding protein 1; ER, endoplasmic reticulum; FOXO, forkhead box O; HSF1, heat shock transcription factor 1; HSP, heat shock protein; HSPA8/ HSC70, heat shock 70kDa protein 8; IL, interleukin; LC3, MAP1LC3, microtubule-associated protein 1 light chain 3; MTMR14/ hJumpy, myotubularin related protein 14; MTOR, mechanistic target of rapamycin; NR1D1/Rev-Erb-a, nuclear receptor subfamily 1, group D, member 1; PBMC, peripheral blood mononuclear cell; PPARGC1A/PGC-1a, peroxisome proliferator-activated receptor, gamma, coactivator 1 a; RHEB, Ras homolog enriched in brain; SOD, superoxide dismutase; SQSTM1/p62, sequestosome 1; TPR, translocated promoter region, nuclear basket protein; TSC, tuberous sclerosis complex; ULK1, unc-51 like autophagy activating kinase 1.Protein quality control (proteostasis) depends on constant protein degradation and resynthesis, and is essential for proper homeostasis in systems from single cells to whole organisms. Cells possess several mechanisms and processes to maintain proteostasis. At one end of the spectrum, the heat shock proteins modulate protein folding and repair. At the other end, the proteasome and autophagy as well as other lysosome-dependent systems, function in the degradation of dysfunctional proteins. In this review, we examine how these systems interact to maintain proteostasis. Both the direct cellular data on heat shock control over autophagy and the time course of exercise-associated changes in humans support the model that heat shock response and autophagy are tightly linked. Studying the links between exercise stress and molecular control of proteostasis provides evidence that the heat shock response and autophagy coordinate and undergo sequential activation and downregulation, and that this is essential for proper proteostasis in eukaryotic systems.

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Section: A Correspondence Between Immune and Muscle Cellsmentioning

confidence: 99%

Heat shock response and autophagy—cooperation and control

2015

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“…13 In carboplatintreated breast cancer cells, transcriptional upregulation of Atg7 was associated with chemoresistance. 14 Conversely, in Down syndrome associated-AML, autophagy is suppressed by mTOR activation. 15 In this context, further Atg7 knockdown resulted in an accumulation of defective mitochondria, DNA damage, and enhanced apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Atg7 suppression enhances chemotherapeutic agent sensitivity and overcomes stroma-mediated chemoresistance in acute myeloid leukemia

Piya¹,

Kornblau²,

Ruvolo³

et al. 2016

Blood

104

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• Atg7 expression is associated with shorter remission duration in AML.• Atg7 inhibition is a proapoptotic phenotype and enhances sensitivity to chemotherapy.Autophagy is a cellular adaptive mechanism to stress, including that induced by chemotherapeutic agents. Reverse phase protein array suggested that high expression of the essential autophagy-related protein, Atg7, was associated with shorter remission in newly diagnosed acute myeloid leukemia (AML) patient samples, indicating a role in chemoresistance. Knockdown of Atg7 in AML cells using short hairpin RNA markedly increased apoptosis and DNA damage following treatment with cytarabine and idarubicin. Interestingly, coculture of AML cells with stromal cells increased autophagy and chemoresistance in the AML cells exposed to chemotherapeutic agents, and this was reversed following Atg7 knockdown. This effect was further enhanced by concomitant knockdown of Atg7 in both AML and stromal cells. These findings strongly suggest that Atg7, and likely microenvironment autophagy in general, plays an important role in AML chemoresistance. Mechanistic studies revealed that Atg7 knockdown induced a proapoptotic phenotype in AML cells, which was manifested by an increased NOXA expression at the transcriptional level. Finally, in a mouse model of human leukemia, Atg7 knockdown extended overall survival after chemotherapy. Thus, the inhibition of Atg7 appears to be a valid strategy to enhance chemosensitivity, and it could indeed improve outcomes in AML therapy. (Blood. 2016;128(9):1260-1269

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“…MDA-MB-231 cells were examined using an MTT assay (6,12,24,48 and 72 h). Rapamycin decreased the viability of MDA-MB-231 breast cancer cells, whereas Atg7 knockdown increased cell viability (Fig.…”

Section: Rapamycin Promotes the Death Of Dha-treated Mda-mb-231 Cellsmentioning

confidence: 99%

“…In recent years, autophagy has been considered to serve an important role in carcinogenesis, development and patient prognosis (12)(13)(14)(15)(16)(17). It has been revealed that several autophagy-related (Atg) genes were involved in autophagosome formation (12)(13)(14)(15)(16)(17). Autophagy is a protective mechanism that exerts antitumor action (13)(14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

“…Autophagy is an intracellular degradation process of dispensable material for cell survival when cells encounter environmental stresses, including nutrient starvation and pathogen infection (11)(12)(13)(14). In recent years, autophagy has been considered to serve an important role in carcinogenesis, development and patient prognosis (12)(13)(14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

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Rapamycin promotes the anticancer action of dihydroartemisinin in breast cancer MDA-MB-231 cells by regulating expression of Atg7 and DAPK

Liu

Zhou

et al. 2018

Oncol Lett

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Abstract. There is limited knowledge regarding the influence of autophagy on the anticancer effect of dihydroartemisinin (DHA). The present study aimed to investigate this influence within human breast cancer cells. Changes in cell viability, cell cycle distribution, apoptosis and associated genes were analyzed in MDA-MB-231 cells subjected to DHA following alteration in autophagy levels; the autophagy level was decreased following autophagy-related 7 (Atg7) knockdown or increased using rapamycin. The data indicated that rapamycin had the ability to notably enhance the anticancer effect of DHA on MDA-MB-231 cells. Autophagy induction may be key in mediating the anticancer effects of DHA, and rapamycin may regulate the death-associated protein kinase via the alteration of Atg7 expression, which would influence cell apoptosis. The present study presented a novel insight into enhancing the effectiveness of future treatment regimens for breast cancer using DHA.

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Heat Shock Factor 1 (HSF1) Controls Chemoresistance and Autophagy through Transcriptional Regulation of Autophagy-related Protein 7 (ATG7)

Cited by 124 publications

References 44 publications

Heat shock response and autophagy—cooperation and control

Heat shock response and autophagy—cooperation and control

Atg7 suppression enhances chemotherapeutic agent sensitivity and overcomes stroma-mediated chemoresistance in acute myeloid leukemia

Rapamycin promotes the anticancer action of dihydroartemisinin in breast cancer MDA-MB-231 cells by regulating expression of Atg7 and DAPK

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