ATP6AP1 promotes cell proliferation and tamoxifen resistance in luminal breast cancer by inducing autophagy

Cell Death and Disease, Год журнала: 2025, Номер 16(1)

Опубликована: Март 25, 2025

Abstract Autophagy is a highly conserved cellular process essential for maintaining homeostasis and influencing cancer development. Lysosomal acidification autophagosome-lysosome fusion are two important steps of autophagy degradation that tightly regulated. Although many key proteins regulate these events have been identified, the effector co-regulate both remain to be explored. ATP6AP1, an accessory subunit V-ATPase, plays critical role in assembly regulation V-ATPase. However, function ATP6AP1 remains unknown, still poorly understood. In this study, we found overexpressed luminal breast tissues promotes proliferation tamoxifen resistance cells vitro vivo. We also observed high expression correlates with poor overall patient survival. Our research further revealed enhances by activating autophagy. Mechanistically, regulating lysosomal fusion. Remarkably, induces through V-ATPase facilitates enhancing interaction between Rab7 HOPS complex. Together, our studies identify as crucial regulator autophagy, potentially serving valuable prognostic marker or therapeutic target human cancer.

Язык: Английский

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Photodynamic and Photothermal Co-Induced Efficient Anti-Tumor Immunotherapy

ACS Applied Materials & Interfaces, Год журнала: 2025, Номер unknown

Опубликована: Март 28, 2025

Currently, immunotherapy based on photothermal and the application of photodynamic therapy in anti-tumor treatment is showing great potential. Its uniqueness lies critical role small molecule immunomodulators promoting effective immune responses against tumors, use laser-activated biophysical mechanisms to precisely trigger swift demise cancer cells, avoiding damage surrounding normal tissues. However, (PDT) alone hampered by tumors' hypoxic environment, resulting poor antitumor effects, while (PTT) cannot arouse enough antigen presentation. It significance design photosensitizers (PSs) that possess both PDT PTT effects. Herein, a series PSs with efficacy are reported, ultimately selecting Cy7-Naph as star due its best overall phototherapeutic effect. Upon reactive oxygen species (ROS) production thermogenesis tumor induced significant apoptosis eventually boosted release damage-associated molecular patterns (DAMPs) under near-infrared (NIR) light irradiation. By combining Toll-like receptor agonist Resiquimod (R848), synergistic for bilateral tumor-bearing mice achieved. This combination promotes dendritic cell (DC) maturation increases infiltration cytotoxic T lymphocytes (CTLs), leading inhibition primary distant tumors.

Язык: Английский

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GCLC desuccinylation regulated by oxidative stress protects human cancer cells from ferroptosis

Cell Death and Differentiation, Год журнала: 2025, Номер unknown

Опубликована: Апрель 5, 2025

Abstract Tumor cells evolve strong antioxidant capacities to counteract the abnormal high level of reactive oxygen species (ROS) in tumor microenvironment. Glutamate-cysteine ligase catalyzing subunit (GCLC) for synthesis glutathione (GSH) represents key enzyme maintain redox homeostasis cells, however, whether its activity is regulated by posttranslational modifications, such as succinylation, remains be clarified. Here, we demonstrate existence succinylation modification on GCLC vitro and vivo assays. NAD-dependent deacetylase Sirtuin-2 (SIRT2) serves desuccinylase catalyzes desuccinylation at sites K38, K126, K326. Specifically, directly interacts with SIRT2, which can substantially enhanced upon ROS treatment. This strengthened association results activation, consequently promoting GSH rendering cancer resistant ferroptosis induction. Depletion SIRT2 decreases total meanwhile increases cellular susceptibility ferroptosis, mostly rescued introducing wild-type GCLC, but not 3K-E mutant. We further demonstrated that histone acetyltransferase P300 succinyltransferase their remarkably decreased after Thus, SIRT2-regulated an essential signaling axis balance coping oxidative stress-induced ferroptosis.

Язык: Английский

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Bromination effect: A new tool to balance increased driving and repulsive forces for building “super-stable” prodrug nano-assemblies

Journal of Controlled Release, Год журнала: 2025, Номер unknown, С. 113699 - 113699

Опубликована: Апрель 1, 2025

Язык: Английский

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Static magnetic field promotes the doxorubicin toxicity effects on osteosarcoma cells

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Апрель 7, 2025

Язык: Английский

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