Oxidized Phospholipids in Tumor Microenvironment Stimulate Tumor Metastasis via Regulation of Autophagy

Seok, Jin Kyung; Hong, Eun-Hee; Yang, Gabsik; Lee, Hye-Eun; Kim, Sin-Eun; Liu, Kwang-Hyeon; Kang, Han Chang; Cho, Yong‐Yeon; Lee, Joo Young

doi:10.3390/cells10030558

Cited by 13 publications

(7 citation statements)

References 56 publications

(33 reference statements)

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“…As the main components of cell membrane, phospholipids are readily oxidized, which leads to increased cellular inflammation, modified cellular metabolism and increased intracellular stress [ 174 ]. Hepatoma and breast cancer cells with high levels of Oxidized Phospholipids (oxPLs) showed increased activation of autophagy, which improved the formation of metastatic lesions by promoting EMT [ 175 ]. In recent years, autophagy has been generally associated with the regulation of chemotherapeutic efficacy.…”

Section: Autophagy and Its Dual Role In The Regulation Of Cancermentioning

confidence: 99%

Molecular Mechanisms of Autophagy in Cancer Development, Progression, and Therapy

et al. 2022

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Autophagy is an evolutionarily conserved and tightly regulated process that plays an important role in maintaining cellular homeostasis. It involves regulation of various genes that function to degrade unnecessary or dysfunctional cellular components, and to recycle metabolic substrates. Autophagy is modulated by many factors, such as nutritional status, energy level, hypoxic conditions, endoplasmic reticulum stress, hormonal stimulation and drugs, and these factors can regulate autophagy both upstream and downstream of the pathway. In cancer, autophagy acts as a double-edged sword depending on the tissue type and stage of tumorigenesis. On the one hand, autophagy promotes tumor progression in advanced stages by stimulating tumor growth. On the other hand, autophagy inhibits tumor development in the early stages by enhancing its tumor suppressor activity. Moreover, autophagy drives resistance to anticancer therapy, even though in some tumor types, its activation induces lethal effects on cancer cells. In this review, we summarize the biological mechanisms of autophagy and its dual role in cancer. In addition, we report the current understanding of autophagy in some cancer types with markedly high incidence and/or lethality, and the existing therapeutic strategies targeting autophagy for the treatment of cancer.

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Section: Autophagy and Its Dual Role In The Regulation Of Cancermentioning

confidence: 99%

Molecular Mechanisms of Autophagy in Cancer Development, Progression, and Therapy

et al. 2022

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“…The inhibitory effect of MHY 1485 on phagolysosome generation has been confirmed in previous studies [59]. In addition, according to Seok et al, 2021, MHY 1485 induces the phosphorylation of mTOR, resulting in a decrease in intracellular LC3, especially the LC3-II form [60]. Therefore, it has been proven that MHY 1485 inhibits autophagy by activating mTOR.…”

Section: Discussionmentioning

confidence: 52%

Regulation of Benzo[a]pyrene-Induced Hepatic Lipid Accumulation through CYP1B1-Induced mTOR-Mediated Lipophagy

Bu,

Kim,

Shin

et al. 2024

IJMS

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Metabolic dysfunction-associated steatotic liver disease (MASLD) is caused by lipid accumulation within the liver. The pathogenesis underlying its development is poorly understood. Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon and a group 1 carcinogen. The aryl hydrocarbon receptor activation by B[a]P induces cytochrome P450 (CYP) enzymes, contributing to hepatic lipid accumulation. However, the molecular mechanism through which the B[a]P-mediated induction of CYP enzymes causes hepatic lipid accumulation is unknown. This research was conducted to elucidate the role of CYP1B1 in regulating B[a]P-induced lipid accumulation within hepatocytes. B[a]P increased hepatic lipid accumulation, which was mitigated by CYP1B1 knockdown. An increase in the mammalian target of rapamycin (mTOR) by B[a]P was specifically reduced by CYP1B1 knockdown. The reduction of mTOR increased the expression of autophagic flux-related genes and promoted phagolysosome formation. Both the expression and translocation of TFE3, a central regulator of lipophagy, were induced, along with the expression of lipophagy-related genes. Conversely, enhanced mTOR activity reduced TFE3 expression and translocation, which reduced the expression of lipophagy-related genes, diminished phagolysosome production, and increased lipid accumulation. Our results indicate that B[a]P-induced hepatic lipid accumulation is caused by CYP1B1-induced mTOR and the reduction of lipophagy, thereby introducing novel targets and mechanisms to provide insights for understanding B[a]P-induced MASLD.

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“…Besides the glucose and amino acids, the lipid affected autophagy regulation also has been found recently [176,177]. The AMPK/mTORC signaling pathway plays an important role in the lipid-related autophagy, indicating that the lipid-regulated tumor autophagy could also associate with AMPK/mTORC [178][179][180][181]. Besides, autophagy can reversely affect lipid metabolism under various situations.…”

Section: Autophagy Derived From Metabolic Activities During Tumorigen...mentioning

confidence: 82%

Crosstalk between metabolism and cell death in tumorigenesis

Yang,

Hu,

Chen

et al. 2024

Mol Cancer

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It is generally recognized that tumor cells proliferate more rapidly than normal cells. Due to such an abnormally rapid proliferation rate, cancer cells constantly encounter the limits of insufficient oxygen and nutrient supplies. To satisfy their growth needs and resist adverse environmental events, tumor cells modify the metabolic pathways to produce both extra energies and substances required for rapid growth. Realizing the metabolic characters special for tumor cells will be helpful for eliminating them during therapy. Cell death is a hot topic of long-term study and targeting cell death is one of the most effective ways to repress tumor growth. Many studies have successfully demonstrated that metabolism is inextricably linked to cell death of cancer cells. Here we summarize the recently identified metabolic characters that specifically impact on different types of cell deaths and discuss their roles in tumorigenesis.

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Oxidized Phospholipids in Tumor Microenvironment Stimulate Tumor Metastasis via Regulation of Autophagy

Cited by 13 publications

References 56 publications

Molecular Mechanisms of Autophagy in Cancer Development, Progression, and Therapy

Molecular Mechanisms of Autophagy in Cancer Development, Progression, and Therapy

Regulation of Benzo[a]pyrene-Induced Hepatic Lipid Accumulation through CYP1B1-Induced mTOR-Mediated Lipophagy

Crosstalk between metabolism and cell death in tumorigenesis

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