TCF12-regulated GRB7 facilitates the HER2+ breast cancer progression by activating Notch1 signaling pathway.

BACKGROUND: Human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC), which accounts for approximately one-fifth of all BCs, are highly invasive with a high rate of recurrence and a poor prognosis. Several studies have shown that growth factor receptor-bound protein 7 (GRB7) might be a potential therapeutic target for tumor diagnosis and prognosis. Nevertheless, the role of GRB7 in HER2+ BC and its underlying mechanisms have not been fully elucidated. The aim of this study was to investigate the biological function and regulatory mechanism of GRB7 in HER2+ BC. METHODS: Bioinformatics analysis was performed using the TCGA, GEO and CancerSEA databases to evaluate the clinical significance of GRB7. RT quantitative PCR, western blot and immunofluorescence were conducted to assess the expression of GRB7 in BC cell lines and tissues. MTT, EdU, colony formation, wound healing, transwell, and xenograft assays were adopted to explore the biological function of GRB7 in HER2+ BC. RNA sequencing was performed to analyze the signaling pathways associated with GRB7 in SK-BR-3 cells after the cells were transfected with GRB7 siRNA. Chromatin immunoprecipitation analysis (ChIP) and luciferase reporter assay were employed to elucidate the potential molecular regulatory mechanisms of GRB7 in HER2+ BC. RESULTS: GRB7 was markedly upregulated and associated with poor prognosis in BC, especially in HER2+ BC. Overexpression of GRB7 increased the proliferation, migration, invasion, and colony formation of HER2+ BC cells, while depletion of GRB7 had the opposite effects in HER2+ BC cells and inhibited xenograft growth. ChIP-PCR and luciferase reporter assay revealed that TCF12 directly bound to the promoter of the GRB7 gene to promote its transcription. GRB7 facilitated HER2+ BC epithelial-mesenchymal transition (EMT) progression by interacting with Notch1 to activate Wnt/ß-catenin pathways and other signaling (i.e., AKT, ERK). Moreover, forced GRB7 overexpression activated Wnt/ß-catenin to promote EMT progression, and partially rescued the inhibition of HER2+ BC proliferation, migration and invasion induced by TCF12 silencing. CONCLUSIONS: Our work elucidates the oncogenic role of GRB7 in HER2+ BC, which could serve as a prognostic indicator and promising therapeutic target.

Preparation and anti-tumor activity of paclitaxel silk protein nanoparticles encapsulated by biofilm.

In order to overcome the poor bioavailability of paclitaxel (PTX), in this study, self-assembled paclitaxel silk fibronectin nanoparticles (PTX-SF-NPs) were encapsulated with outer membrane vesicles of Escherichia coli (E. coil), and biofilm-encapsulated paclitaxel silk fibronectin nanoparticles (OMV-PTX-SF-NPs) were prepared by high-pressure co-extrusion, the size and zeta potential of the OMV-PTX-SF-NPs were measured. The antitumor effects of OMV-PTX-SF-NPs were evaluated by cellular and pharmacodynamic assays, and pharmacokinetic experiments were performed. The results showed that hydrophobic forces and hydrogen bonding played a major role in the interaction between paclitaxel and filipin proteins, and the size of OMV-PTX-SF-NPs was 199.8 ± 2.8 nm, zeta potential was -17.8 ± 1.3 mv. The cellular and in vivo pharmacokinetic assays demonstrated that the OMV-PTX-SF-NPs possessed a promising antitumor effect. Pharmacokinetic experiments showed that the AUC0-∞ of OMV-PTX-SF-NPs was 5.314 ± 0.77, which was much larger than that of free PTX, which was 0.744 ± 0.14. Overall, we have successfully constructed a stable oral formulation of paclitaxel with a sustained-release effect, which is able to effectively increase the bioavailability of paclitaxel, improve the antitumor activity, and reduce the adverse effects.

Albumin Nanoparticle-Based Drug Delivery Systems.

Nanoparticle-based systems are extensively investigated for drug delivery. Among others, with superior biocompatibility and enhanced targeting capacity, albumin appears to be a promising carrier for drug delivery. Albumin nanoparticles are highly favored in many disease therapies, as they have the proper chemical groups for modification, cell-binding sites for cell adhesion, and affinity to protein drugs for nanocomplex generation. Herein, this review summarizes the recent fabrication techniques, modification strategies, and application of albumin nanoparticles. We first discuss various albumin nanoparticle fabrication methods, from both pros and cons. Then, we provide a comprehensive introduction to the modification section, including organic albumin nanoparticles, metal albumin nanoparticles, inorganic albumin nanoparticles, and albumin nanoparticle-based hybrids. We finally bring further perspectives on albumin nanoparticles used for various critical diseases.

Albumin appears to be a promising carrier for drug delivery with superior biocompatibility and enhanced targeting capacity. This review focuses on the importance of albumin nanoparticles in drug delivery and concludes the recent fabrication techniques to prepare albumin nanoparticles, the modification strategies to require functional albumin nanoparticles, and critical applications of albumin nanoparticles in various diseases. The aim of this review is to help readers understand the significant potential of albumin nanoparticles in drug delivery.

Metagenomic and metabolomic analysis showing the adverse risk-benefit trade-off of the ketogenic diet.

BACKGROUND: Ketogenic diets are increasingly popular for addressing obesity, but their impacts on the gut microbiota and metabolome remain unclear. This paper aimed to investigate how a ketogenic diet affects intestinal microorganisms and metabolites in obesity. METHODS: Male mice were provided with one of the following dietary regimens: normal chow, high-fat diet, ketogenic diet, or high-fat diet converted to ketogenic diet. Body weight and fat mass were measured weekly using high-precision electronic balances and minispec body composition analyzers. Metagenomics and non-targeted metabolomics data were used to analyze differences in intestinal contents. RESULTS: Obese mice on the ketogenic diet exhibited notable improvements in weight and body fat. However, these were accompanied by a significant decrease in intestinal microbial diversity, as well as an increase in Firmicutes abundance and a 247% increase in the Firmicutes/Bacteroidetes ratio. The ketogenic diet also altered multiple metabolic pathways in the gut, including glucose, lipid, energy, carbohydrate, amino acid, ketone body, butanoate, and methane pathways, as well as bacterial secretion and colonization pathways. These changes were associated with increased intestinal inflammation and dysbiosis in obese mice. Furthermore, the ketogenic diet enhanced the secretion of bile and the synthesis of aminoglycoside antibiotics in obese mice, which may impair the gut microbiota and be associated with intestinal inflammation and immunity. CONCLUSIONS: The study suggest that the ketogenic diet had an unfavorable risk-benefit trade-off and may compromise metabolic homeostasis in obese mice.

INPP4B suppresses HER2-induced mesenchymal transition in HER2+ breast cancer and enhances sensitivity to Lapatinib.

Human epidermal growth factor receptor 2 positive (HER2+) breast cancer (BC) tends to metastasize and has a bad prognosis due to its high malignancy and rapid progression. Inositol polyphosphate 4-phosphatase isoenzymes type II (INPP4B) plays unequal roles in the development of various cancers. However, the function of INPP4B in HER2+ BC has not been elucidated. Here we found that INPP4B expression was significantly lower in HER2+ BC and positively correlated with the prognosis by bioinformatics and tissue immunofluorescence analyses. Overexpression of INPP4B inhibited cell proliferation, migration, and growth of xenografts in HER2+ BC cells. Conversely, depletion of INPP4B reversed these effects and activated the PDK1/AKT and Wnt/ß-catenin signaling pathways to promote epithelial-mesenchymal transition (EMT) progression. Moreover, INPP4B overexpression blocked epidermal growth factor (EGF) -induced cell proliferation, migration and EMT progression, whereas INPP4B depletion antagonized HER2 depletion in reduction of cell proliferation and migration of HER2+ BC cells. Additionally, Lapatinib (LAP) inhibited HER2+ BC cell survival, proliferation and migration, and its effect was further enhanced by overexpression of INPP4B. In summary, our results illustrate that INPP4B suppresses HER2+ BC growth, migration and EMT, and its expression level affects patient outcome, further providing new insights into clinical practice.

A Light-Responsive Neural Circuit Suppresses Feeding.

Light plays an essential role in a variety of physiological processes, including vision, mood, and glucose homeostasis. However, the intricate relationship between light and an animal's feeding behavior has remained elusive. Here, we found that light exposure suppresses food intake, whereas darkness amplifies it in male mice. Interestingly, this phenomenon extends its reach to diurnal male Nile grass rats and healthy humans. We further show that lateral habenula (LHb) neurons in mice respond to light exposure, which in turn activates 5-HT neurons in the dorsal Raphe nucleus (DRN). Activation of the LHb→5-HTDRN circuit in mice blunts darkness-induced hyperphagia, while inhibition of the circuit prevents light-induced anorexia. Together, we discovered a light-responsive neural circuit that relays the environmental light signals to regulate feeding behavior in mice.

LncRNA taurine upregulated gene 1 in liver disease.

Long non-coding RNAs (lncRNAs) are RNA sequences exceeding 200 nucleotides in length that lack protein-coding capacity and participate in diverse biological processes in the human body, particularly exerting a pivotal role in disease surveillance, diagnosis, and progression. Taurine upregulated gene 1 (TUG1) is a versatile lncRNA, and recent studies have revealed that the aberrant expression or function of TUG1 is intricately linked to the pathogenesis of liver diseases. Consequently, we have summarized the current understanding of the mechanism of TUG1 in liver diseases such as liver fibrosis, fatty liver, cirrhosis, liver injury, hepatitis, and liver cancer. Moreover, mounting evidence suggests that interventions targeting TUG1 or its downstream pathways may hold therapeutic promise for liver diseases. This review elucidates the characteristics, mechanisms, and targets of TUG1 in liver diseases, offering a theoretical basis for the prevention, diagnosis, treatment, and prognostic biomarkers of liver diseases.

Forest management positively reshapes the phyllosphere bacterial community and improves community stability.

Research has shown that forest management can improve the post-drought growth and resilience of Qinghai spruce in the eastern Qilian Mountains, located on the northeastern Tibetan Plateau. However, the impact of such management on the tree-associated phyllosphere microbiome is not yet fully understood. This study provides new evidence of positive forest management effects on the phyllosphere microbiome after extreme drought, from the perspectives of community diversity, structure, network inference, keystone species, and assembly processes. In managed Qinghai spruce forest, the α-diversity of the phyllosphere bacterial communities increased, whereas the ß-diversity decreased. In addition, the phyllosphere bacterial community became more stable and resistant, yet less complex, following forest management. Keystone species inferred from a bacterial network also changed under forest management. Furthermore, forest management mediated changes in community assembly processes, intensifying the influence of determinacy, while diminishing that of stochasticity. These findings support the hypothesis that management can re-assemble the phyllosphere bacterial community, enhance community stability, and ultimately improve tree growth. Overall, the study highlights the importance of forest management on the phyllosphere microbiome and furnishes new insights into forest conservation from the perspective of managing microbial processes and effects.

Human Pluripotent Stem Cell Derived Organoids Reveal a Role for WNT Signaling in Dorsal-Ventral Patterning of the Hindgut.

The cloaca is a transient structure that forms in the terminal hindgut giving rise to the rectum dorsally and the urogenital sinus ventrally. Similarly, human hindgut cultures derived from human pluripotent stem cells generate human colonic organoids (HCOs) which also contain co-developing urothelial tissue. In this study, our goal was to identify pathways involved in cloacal patterning and apply this to human hindgut cultures. RNA-seq data comparing dorsal versus ventral cloaca in e10.5 mice revealed that WNT signaling was elevated in the ventral versus dorsal cloaca. Inhibition of WNT signaling in hindgut cultures biased their differentiation towards a colorectal fate. WNT activation biased differentiation towards a urothelial fate, giving rise to human urothelial organoids (HUOs). HUOs contained cell types present in human urothelial tissue. Based on our results, we propose a mechanism whereby WNT signaling patterns the ventral cloaca, prior to cloacal septation, to give rise to the urogenital sinus.

Chitosan-based fluorescent probe for the detection of Fe3+ in real water and food samples.

Iron ions play a crucial role in the environment and the human body. Therefore, developing an effective detection method is crucial. In this paper, we report CNS2, a chitosan-based fluorescent probe utilizing naphthalimide as a fluorophore. CNS2 is designed to "quench" its own yellow fluorescence through the specific binding of compounds containing enol structures to Fe3+. Studying the fluorescence lifetime of CNS2 in the presence or absence of Fe3+ reveals that the quenching mechanism is static. The presence of multiple recognition sites on the chitosan chain bound to Fe3+ gave CNS2 rapid recognition (1 min) and high sensitivity, with a detection limit as low as 0.211 µM. Moreover, the recognition of Fe3+ by CNS2 had a good specificity and was not affected by interferences. More importantly, in this study, CNS2 was successfully utilised to prepare fluorescent composite membranes and to detect Fe3+ in real water samples and a variety of food samples. The results show that the complex sample environment still does not affect the recognition of Fe3+ by CNS2. All the above experiments obtained more satisfactory results, which provide strong support for the detection of Fe3+ by the probe CNS2 in practical applications.

Tough and Strain-Sensitive Organohydrogels Based on MXene and PEDOT/PSS and Their Effects on Mechanical Properties and Strain-Sensing Performance.

Conductive hydrogels have shown promising application prospects in the field of flexible sensors, but they often suffer from poor mechanical properties, low sensitivity, and lack of frost resistance. Herein, we report a tough, highly sensitive, and antifreeze strain sensor assembled from a conductive organohydrogel composed of a dual-cross-linked polyacrylamide and poly(vinyl alcohol) (PVA) network, as well as MXene nanosheets as nanofillers and poly(3,4-ethylenedioxythiophene)-doped poly(styrenesulfonate) (PEDOT/PSS) as the main conducting component (PPMP-OH organohydrogel). The tensile strength and toughness of PPMP-OH had been greatly enhanced by MXene nanosheets due to the mechanical reinforcement of MXene nanosheets, as well as various strong noncovalent interactions formed in the organohydrogels. The PPM1P-OH organohydrogels showed a tensile strength of 1.48 MPa at 772% and a toughness of 5.59 MJ/m3. Moreover, the conductivity and strain-sensing performance of PPMP-OH were significantly improved by PEDOT/PSS, which can form hydrogen bonds with PVA and electrostatic interactions with MXene. This was greatly beneficial for constructing a uniformly distributed and stable 3D conductive network and helped to obtain strain-dependent resistance of PPMP-OH. The strain sensors assembled from PPMP1-OH exhibited a high sensitivity of 5.16, a wide range of detectable strains up to 500%, and a short response time of 122 ms, which can effectively detect various physiological activities of the human body with high stability. In addition, the corresponding pressure sensor array also showed high sensitivity in identifying pressure magnitude and position.

CCT020312 exerts anti-prostate cancer effect by inducing G1 cell cycle arrest, apoptosis and autophagy through activation of PERK/eIF2α/ATF4/CHOP signaling.

PERK/eIF2α/ATF4/CHOP signaling pathway is one of three major branches of unfolded protein response (UPR) and has been implicated in tumor progression. CCT020312 is a selective PERK activator and may have a potential anti-tumor effect. Here we investigated the anti-prostate cancer effect and its underlying mechanism of CCT020312. Our results showed that CCT020312 inhibited prostate cancer cell viability by inducing cell cycle arrest, apoptosis and autophagy through activation of PERK/eIF2α/ATF4/CHOP signaling. CCT020312 treatment caused cell cycle arrest at G1 phase and increased the levels of cleaved-Caspase3, cleaved-PARP and Bax in prostate cancer C4-2 and LNCaP cells. Moreover, CCT020312 increased LC3II/I, Atg12-Atg5 and Beclin1 levels and induced autophagosome formation. Furthermore, knockdown of CHOP reversed CCT020312-induced cell viability decrease, apoptosis and autophagy. Bafilomycin A1 reversed CCT020312-induced cell viability decrease but had no effect on CCT020312-induced CHOP activation in C4-2 and LNCaP cells. In vivo, CCT020312 suppressed tumor growth in C4-2 cells-derived xenograft mouse model, activated PERK pathway, and induced autophagy and apoptosis. Our study illustrates that CCT020312 exerts an anti-tumor effect in prostate cancer via activating the PERK pathway, thus indicating that CCT020312 may be a potential drug for prostate cancer.

Development of functional resident macrophages in human pluripotent stem cell-derived colonic organoids and human fetal colon.

Most organs have tissue-resident immune cells. Human organoids lack these immune cells, which limits their utility in modeling many normal and disease processes. Here, we describe that pluripotent stem cell-derived human colonic organoids (HCOs) co-develop a diverse population of immune cells, including hemogenic endothelium (HE)-like cells and erythromyeloid progenitors that undergo stereotypical steps in differentiation, resulting in the generation of functional macrophages. HCO macrophages acquired a transcriptional signature resembling human fetal small and large intestine tissue-resident macrophages. HCO macrophages modulate cytokine secretion in response to pro- and anti-inflammatory signals and were able to phagocytose and mount a robust response to pathogenic bacteria. When transplanted into mice, HCO macrophages were maintained within the colonic organoid tissue, established a close association with the colonic epithelium, and were not displaced by the host bone-marrow-derived macrophages. These studies suggest that HE in HCOs gives rise to multipotent hematopoietic progenitors and functional tissue-resident macrophages.

Effects of an Omaha System-based follow-up regimen on self-care and quality of life in gastrointestinal surgery patients.

BACKGROUND: Currently, a variety of new nursing methods and routine nursing have been widely used in the nursing of gastrointestinal surgery patients. AIM: To investigate the effect of follow-up protocol based on the Omaha System on self-care ability and quality of life of gastrointestinal surgery patients. METHODS: A total of 128 patients with inflammatory bowel disease in gastrointestinal surgery in gastrointestinal surgery from March 2019 to August 2021 were divided into A (n = 64) and B (n = 64) groups according to different nursing methods. The group A received a follow-up program Omaha System-based intervention of the group B, whereas the group B received the routine nursing intervention. Medical Coping Modes Questionnaire, Crohn's and Colitis Knowledge Score (CCKNOW), inflammatory bowel disease questionnaire (IBDQ), Exercise of Self-nursing Agency Scale (ESCA), The Modified Mayo Endoscopic Score, and Beliefs about Medicine Questionnaire (BMQ) were compared between the two groups. RESULTS: Following the intervention, the group A were facing score significantly increased than group B, while the avoidance and yield scores dropped below of group B (all P < 0.05); in group A, the level of health knowledge, personal care abilities, self-perception, self-awareness score and ESCA total score were more outstanding than group B (all P < 0.05); in group A the frequency of defecation, hematochezia, endoscopic performance, the total evaluation score by physicians and the disease activity were lower than group B (all P < 0.05); in the group A, the total scores of knowledge in general, diet, drug, and complication and CCKNOW were higher than group B (all P < 0.05); in group A, the necessity of taking medicine, score of medicine concern and over-all score of BMQ were more significant than group B (all P < 0.05); at last in the group A, the scores of systemic and intestinal symptoms, social and emotional function, and IBDQ in the group A were higher than group B (all P < 0.05). CONCLUSION: For gastrointestinal surgery patients, the Omaha System-based sequel protocol can improve disease awareness and intervention compliance, help them to face the disease positively, reduce disease activity, and improve patients' self-nursing ability and quality of life.

CEP55 as a Promising Immune Intervention Marker to Regulate Tumor Progression: A Pan-Cancer Analysis with Experimental Verification.

CEP55, a member of the centrosomal protein family, affects cell mitosis and promotes the progression of several malignancies. However, the relationship between CEP55 expression levels and prognosis, as well as their role in cancer progression and immune infiltration in different cancer types, remains unclear. We used a combined form of several databases to validate the expression of CEP55 in pan-cancer and its association with immune infiltration, and we further screened its targeted inhibitors with CEP55. Our results showed the expression of CEP55 was significantly higher in most tumors than in the corresponding normal tissues, and it correlated with the pathological grade and age of the patients and affected the prognosis. In breast cancer cells, CEP55 knockdown significantly decreased cell survival, proliferation, and migration, while overexpression of CEP55 significantly promoted breast cancer cell proliferation and migration. Moreover, CEP55 expression was positively correlated with immune cell infiltration, immune checkpoints, and immune-related genes in the tumor microenvironment. CD-437 was screened as a potential CEP55-targeted small-molecule compound inhibitor. In conclusion, our study highlights the prognostic value of CEP55 in cancer and further provides a potential target selection for CEP55 as a potential target for intervention in tumor immune infiltration and related immune genes.

Series Arc Fault Detection Based on Multimodal Feature Fusion.

In low-voltage distribution systems, the load types are complex, so traditional detection methods cannot effectively identify series arc faults. To address this problem, this paper proposes an arc fault detection method based on multimodal feature fusion. Firstly, the different mode features of the current signal are extracted by mathematical statistics, Fourier transform, wavelet packet transform, and continuous wavelet transform. The different modal features include one-dimensional features, such as time-domain features, frequency-domain features, and wavelet packet energy features, and two-dimensional features of time-spectrum images. Secondly, the extracted features are preprocessed and prioritized for importance based on different machine learning algorithms to improve the feature data quality. The features of higher importance are input into an arc fault detection model. Finally, an arc fault detection model is constructed based on a one-dimensional convolutional network and a deep residual shrinkage network to achieve high accuracy. The proposed detection method has higher detection accuracy and better performance compared with the arc fault detection method based on single-mode features.

Methionine enkephalin inhibited cervical cancer migration as well as invasion and activated CD11b+ NCR1+ NKs of tumor microenvironment.

This study was to study the role of methionine enkephalin (menk) in cell invasion and migration as well as NK cells activation of tumor microenvironment in cervical cancer. The results showed that menk inhibited cervical cancer migration and invasion. In addition, we found menk affected epithelial to mesenchymal transition (EMT) related indicators, with increasing E-cadherin level, decreasing N-cadherin and vimentin level. Through in vivo mouse model, we found that menk IFNγ and NKP46 expression was upregulated in tumor tissues by menk compared with controls, while LAG3 expression was inhibited by menk, besides, there was an upregulation of CD11b+ NCR1+ NKs of tumor microenvironment in cervical cancer. Therefore, we concluded that menk inhibited cancer migration and invasion via affecting EMT related indicators and activated CD11b+ NCR1+ NKs of tumor microenvironment in cervical cancer, laying a theoretical foundation for the further clinical treatment of menk.

N76-1, a novel CDK7 inhibitor, exhibits potent anti-cancer effects in triple negative breast cancer.

Emerging evidence suggests that genetically highly specific triple-negative breast cancer (TNBC) possesses a relatively uniform transcriptional program that is abnormally dependent on cyclin-dependent kinase 7 (CDK7). In this study, we obtained an inhibitor of CDK7, N76-1, by attaching the side chain of the covalent CDK7 inhibitor THZ1 to the core of the anaplastic lymphoma kinase inhibitor ceritinib. This study aimed to elucidate the role and underlying mechanism of N76-1 in TNBC and evaluate its potential value as an anti-TNBC drug. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays showed that N76-1 inhibited the viability of TNBC cells. Kinase activity and cellular thermal shift assays showed that N76-1 directly targeted CDK7. Flow cytometry results revealed that N76-1 induced apoptosis and cell cycle arrest in the G2/M phase. N76-1 also effectively inhibited the migration of TNBC cells by high-content detection. The RNA-seq analysis showed that the transcription of genes, especially those related to transcriptional regulation and cell cycle, was suppressed after N76-1 treatment. Moreover, N76-1 markedly inhibited the growth of TNBC xenografts and phosphorylation of RNAPII in tumor tissues. In summary, N76-1 exerts potent anticancer effects in TNBC by inhibiting CDK7 and provides a new strategy and research basis for the development of new drugs for TNBC.

VPS34-IN1 induces apoptosis of ER+ breast cancer cells via activating PERK/ATF4/CHOP pathway.

VPS34-IN1 is a specific selective inhibitor of Class III Phosphatidylinositol 3-kinase (PI3K) and has been shown to exhibit a significant antitumor effect in leukemia and liver cancer. In current study, we focused on the anticancer effect and potential mechanism of VPS34-IN1 in estrogen receptor positive (ER+ ) breast cancer. Our results revealed that VPS34-IN1 inhibited the viability of ER+ breast cancer cells in vitro and in vivo. Flow cytometry and western blot analyses showed that VPS34-IN1 treatment induced breast cancer cell apopotosis. Interestingly, VPS34-IN1 treatment activated protein kinase R (PKR)-like ER kinase (PERK) branch of endoplasmic reticulum (ER) stress. Furthermore, knockdown of PERK by siRNA or inhibition of PERK activity by chemical inhibitor GSK2656157 could attenuate VPS34-IN1-mediated apoptosis in ER+ breast cancer cells. Collectively, VPS34-IN1 has an antitumor effect in breast cancer, and it may result from activating PERK/ATF4/CHOP pathway of ER stress to induce cell apoptosis. These findings broaden our understanding of the anti-breast cancer effects and mechanisms of VPS34-IN1 and provide new ideas and reference directions for the treatment of ER+ breast cancer.