• The Korean Journal of Physiology and Pharmacology
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• 제28권4호
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• pp.379-387
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• 2024

Breast cancer (BC) is most commonly diagnosed worldwide. Liquiritigenin is a flavonoid found in various species of the Glycyrrhiza genus, showing anti-tumor activity. This article was to explore the influences of liquiritigenin on the biological behaviors of BC cells and its underlying mechanism. BC cells were treated with liquiritigenin alone or transfected with oe-HSP90 before liquiritigenin treatment. RT-qPCR and Western blotting were employed to examine the levels of HSP90, Snail, E-cadherin, HSC70, and LAMP-2A. Cell viability, proliferation, migration, and invasion were evaluated by performing MTT, colony formation, scratch, and Transwell assays, respectively. Liquiritigenin treatment reduced HSP90 and Snail levels and enhanced E-cadherin expression as well as inhibiting the proliferation, migration, and invasion of BC cells. Moreover, liquiritigenin treatment decreased the expression of HSC70 and LAMP-2A, proteins related to chaperone-mediated autophagy (CMA). HSP90 overexpression promoted the CMA, invasion, and migration of BC cells under liquiritigenin treatment. Liquiritigenin inhibits HSP90-mediated CMA, thereby suppressing BC cell growth.

• BMB Reports
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• 제49권6호
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• pp.337-343
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• 2016

Understanding of trafficking, processing, and degradation mechanisms of amyloid precursor protein (APP) is important because APP can be processed to produce β-amyloid (Aβ), a key pathogenic molecule in Alzheimer's disease (AD). Here, we found that APP contains KFERQ motif at its C-terminus, a consensus sequence for chaperone-mediated autophagy (CMA) or microautophagy which are another types of autophagy for degradation of pathogenic molecules in neurodegenerative diseases. Deletion of KFERQ in APP increased C-terminal fragments (CTFs) and secreted N-terminal fragments of APP and kept it away from lysosomes. KFERQ deletion did not abolish the interaction of APP or its cleaved products with heat shock cognate protein 70 (Hsc70), a protein necessary for CMA or microautophagy. These findings suggest that KFERQ motif is important for normal processing and degradation of APP to preclude the accumulation of APP-CTFs although it may not be important for CMA or microautophagy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권14호
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• pp.5715-5719
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• 2014

Autophagy is crucial in the maintenance of homeostasis and regenerated energy of mammalian cells. Macroautophagy and chaperone-mediated autophagy(CMA) are the two best-identified pathways. Recent research has found that in normal cells, decline of macroautophagy is appropriately parallel with activation of CMA. However, whether it is also true in cancer cells has been poorly studied. Here we focused on cross-talk and conversion between macroautophagy and CMA in cultured Burkitt lymphoma Raji cells when facing serum deprivation and exposure to a toxic compound, arsenic trioxide. The results showed that both macroautophagy and CMA were activated sequentially instead of simultaneously in starvation-induced Raji cells, and macroautophagy was quickly activated and peaked during the first hours of nutrition deprivation, and then gradually decreased to near baseline. With nutrient deprivation persisted, CMA progressively increased along with the decline of macroautophagy. On the other hand, in arsenic trioxide-treated Raji cells, macroautophagy activity was also significantly increased, but CMA activity was not rapidly enhanced until macroautophagy was inhibited by 3-methyladenine, an inhibitor. Together, we conclude that cancer cells exhibit differential responses to diverse stressor-induced damage by autophagy. The sequential switch of the first-aider macroautophagy to the homeostasis-stabilizer CMA, whether active or passive, might be conducive to the adaption of cancer cells to miscellaneous intracellular or extracellular stressors. These findings must be helpful to understand the characteristics, compensatory mechanisms and answer modes of different autophagic pathways in cancer cells, which might be very important and promising to the development of potential targeting interventions for cancer therapies via regulation of autophagic pathways.

• BMB Reports
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• 제56권4호
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• pp.252-257
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• 2023

The hypoxia-inducible factor-1α (HIF-1α) is a key regulator of hypoxic stress under physiological and pathological conditions. HIF-1α protein stability is tightly regulated by the ubiquitin-proteasome system (UPS) and autophagy in normoxia, hypoxia, and the tumor environment to mediate the hypoxic response. However, the mechanisms of how the UPS and autophagy interplay for HIF-1α proteostasis remain unclear. Here, we found a HIF-1α species propionylated at lysine (K) 709 by p300/CREB binding protein (CBP). HIF-1α stability and the choice of degradation pathway were affected by HIF-1α propionylation. K709-propionylation prevented HIF-1α from degradation through the UPS, while activated chaperon-mediated autophagy (CMA) induced the degradation of propionylated and nonpropionylated HIF-1α. CMA contributed to HIF-1α degradation in both normoxia and hypoxia. Furthermore, the pan-cancer analysis showed that CMA had a significant positive correlation with the hypoxic signatures, whereas SIRT1, responsible for K709-depropionylation correlated negatively with them. Altogether, our results revealed a novel mechanism of HIF-1α distribution into two different degradation pathways.

• Tuberculosis and Respiratory Diseases
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• 제80권1호
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• pp.83-89
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• 2017

Background: Previous studies report that apoptosis and autophagy are involved in the pathogenesis of emphysema, and macroautophagy is one of the processes regulating the apoptosis pathway. However, few studies have evaluated whether chaperone-mediated autophagy (CMA) contributes to the regulation of apoptosis. In this study, we investigated the impact of autophagy, including both macroautophagy and CMA, on the apoptosis in bronchial epithelial cells. Methods: Cigarette smoke extract (CSE) was injected intratracheally into C57BL/6 mice, and emphysema and apoptosis were evaluated in the lungs. After treatment with CSE, apoptosis, macroautophagy, and CMA were measured in BEAS2-B cells, and the impact of autophagy on the apoptosis was evaluated following knockdown of autophagy-related genes by short interfering RNAs (siRNAs). Results: Intratracheal CSE injection resulted in the development of emphysema and an increase in apoptosis in mice. CSE increased the apoptosis in BEAS2-B cells, and also elevated the expression of proteins related to both macroautophagy and CMA in BEAS2-B cells. The knockdown experiment with siRNAs showed that macroautophagy increases apoptosis in BEAS2-B cells, while CMA suppresses apoptosis. Conclusion: The intratracheal injection of CSE induces pulmonary emphysema and an increase in apoptosis in mice. CSE also induces apoptosis, macroautophagy, and CMA of bronchial epithelial cells. Macroautophagy and CMA regulate apoptosis in opposite directions.