International journal of oncology最新文献

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, for the scratch‑wound assay experiments shown in Fig. 6 on p. 2318, the 'control siRNA/24 h' and 'podoplanin siRNA/48 h' panels contained an overlapping section of data; such that these data, which were intended to show the results from differently performed experiments, appeared to have been derived from the same original source. Upon analyzing the data independently in the Editorial Office, it came to light that, in addition to control blots, the podoplanin blots were duplicated in Fig. 2A and B, and also in Fig. 3A and B, although it wasn't clear whether this was simply the way in which the authors had chosen to arrange the data in these figures, as the reported experimental conditions were the same in the respective figure parts. The authors were contacted by the Editorial Office to offer an explanation for these possible anomalies in the presentation of the data in this paper, although up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office conitnues to investigate this matter further. [International Journal of Oncology 48: 2310‑2320, 2016; DOI: 10.3892/ijo.2016.3445].

Following the publication of the above paper, a concerned reader drew to the Editor's attention that, for the immuno-histochemistry images shown in Fig. 6, the Control/PCNA and Control/p27kip1 panels appeared to be duplicates of each other, where the results of differently performed experiments were intended to have been portrayed. The authors were contacted by the Editorial Office to offer an explanation for this potential anomaly in the presentation of the data in this paper, although up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [International Journal of Oncology 36: 913‑920, 2010; DOI: 10.3892/ijo_00000570].

Adipocytes represent the most prominent component of breast tissue stroma and are recognized as significant contributors to the observed association between obesity and breast cancer (BC). It has been widely reported that dysfunctional adipose tissue in obesity has a profound effect on the biology of BC via the secretion of several bioactive molecules. Recently, extracellular vesicles (EVs), a heterogeneous group of membrane‑enclosed structures, have been recognized as key players in adipocyte‑BC cell communication. We previously demonstrated that adipocyte‑derived EVs promoted BC proliferation, migration, invasion, stemness and traits of epithelial‑to‑mesenchymal transition through the activation of hypoxia inducible factor‑1α (HIF‑1α). The present study, to further understand the impact of EVs in breast adiponcosis, investigated the effects of adipocyte‑derived EVs on the BC proteome. By employing liquid chromatography‑tandem mass spectrometry and different bioinformatic tools (such as Proteomap, STRING, FunRich, Reactome and MsigDB), it was found that adipocyte‑derived EVs regulated the expression of multiple proteins implicated in metabolic processes. Adipocyte‑derived EVs shifted cell metabolism towards oxidative phosphorylation in estrogen receptor‑positive (ER+) BC cell lines, including MCF‑7, ZR‑75‑1 and BT‑474 BC cells, through an increased mitochondrial activity along with an enhanced ATP production. These findings were extended by treating BC cells with EVs isolated from the serum of patients with BC classified as normal weight (NW‑EVs) and overweight or obese (OW/Ob‑EVs). Treatment of BC cells with OW/Ob‑EVs resulted in a significant increase of mitochondrial activity and ATP production compared with NW‑EVs. Of note, inhibition of HIF‑1α expression/activity reversed the effects of both adipocyte‑derived EVs and OW/Ob‑EVs on BC cell metabolism. In conclusion, the present study underscored the pivotal role of EVs in the BC‑obesity link, highlighting their involvement in driving metabolic reprogramming in ER+ BC cells through HIF‑1α.

The occurrence and development of tumors is affected by tumor cells themselves and various components of the tumor microenvironment (TME). Among these, cancer‑associated fibroblasts (CAFs), the main stromal component, can differentiate from different cell types and play an important role in the TME. The present review summarized the role of the metabolic reprogramming of CAFs in tumor development and progression. As the rapid growth of tumors is a process inseparable from energy supply and the TME is characterized by hypoxia and nutrient deficiencies, metabolic reprogramming can reverse the effects of a lack of energy supply in the TME. Studies have found that CAFs can affect tumor proliferation, migration, invasion, metastasis and drug resistance by changing metabolic patterns. The present review promoted research on the metabolic reprogramming of CAFs and emphasized the importance of considering the heterogeneity and plasticity of CAFs in the TME, which will lead to the development of more effective therapeutic strategies that target specific metabolic pathways in CAFs, potentially improving the efficacy of cancer treatments and overcoming drug resistance.

Triple‑negative breast cancer (TNBC) is a subtype of breast cancer, known for its poor prognosis due to its high invasiveness, strong metastatic tendencies and propensity for recurrence. Epithelial to mesenchymal transition (EMT) is a crucial process in tumor invasion and metastasis and in the formation of cancer‑initiating cells. Hutchinson‑Gilford progeria is a rare condition characterized by accelerated aging, caused by a mutated form of lamin A, known as progerin. The present study aimed to investigate the effect of progerin overexpression on TNBC and uncover its underlying mechanisms of action. Therefore, cell senescence was assessed using senescence‑associated β‑galactosidase staining, while cell proliferation was measured by colony formation, Cell Counting Kit‑8 and EdU assays. Additionally, cell metastasis was evaluated using wound‑healing, Transwell and cell adhesion assays. Immunofluorescence staining was carried out to observe actin cytoskeleton and nuclear morphology. The results showed that progerin markedly suppressed the colony formation, migration, invasion and adhesion abilities of BT‑549 and MDA‑MB‑231 TNBC cell lines, without affecting cell senescence or proliferation. In addition, progerin overexpression altered nuclear morphology and actin cytoskeleton organization in TNBC cells. Furthermore, the expression levels of the mesenchymal markers, N‑cadherin, vimentin, Snail and Slug, were reduced, while those of the epithelial marker, E‑cadherin, were enhanced in TNBC cells. Overall, the results of the present study suggested that progerin overexpression could inhibit TNBC cell metastasis, probably via actin cytoskeleton remodeling and regulate the expression levels of the cytoskeletal‑related proteins, anillin and β‑catenin, and those of the EMT‑related ones. The aforementioned findings could provide novel insights into the identification of potential molecular targets for breast cancer therapy.

Cancers are not merely composed of tumor cells; rather, they constitute a complex tumor microenvironment (TME) comprising diverse cell types and noncellular factors. Extracellular matrix (ECM) represents a critical component of the TME. Fibulin2 participates in ECM formation in various tumors, and its altered expression in multiple malignancies can affect tumor cell proliferation and invasiveness. Additionally, Fibulin2 has emerged as a potential biomarker in various cancer types and serves a pivotal role in tumor progression. Consequently, therapeutic strategies targeting Fibulin2 hold considerable promise. However, the research and development of Fibulin2‑targeted therapeutics has progressed at a relatively slow pace. Therefore, the roles and mechanisms of Fibulin2 in various malignancies, along with investigations into its utility as a biomarker, are comprehensively discussed in the present review. This may provide valuable guidance for the clinical translation and application of Fibulin2‑targeted therapies, and the utilization of Fibulin2 as a predictive biomarker.

Triple‑negative breast cancer (TNBC) is an aggressive malignancy with limited treatment options, leading to poor clinical outcomes and the need for novel therapeutic approaches. Nintedanib, a United States Food and Drug Administration‑approved multi‑kinase inhibitor with anti‑fibrotic and anti‑angiogenic properties, has shown promise in cancer treatment. However, its precise molecular effects on TNBC have not yet been fully elucidated. Therefore, the present study aimed to investigate the therapeutic potential of nintedanib in TNBC using in vitro and in vivo models, specifically focusing on its regulatory effects on key oncogenic pathways. The present study utilized TNBC cell lines (MDA‑MB‑231 and 4T1) and BALB/c mice to evaluate the antitumor efficacy of nintedanib. Cell viability and clonogenic capacity were assessed using Cell Counting Kit‑8 and colony formation assays. Subsequently, apoptosis induction and cell cycle progression were determined by flow cytometry, and cell migration and invasion were analyzed through scratch and Transwell assays. To identify underlying mechanisms, potential molecular targets were identified via bioinformatics and network pharmacology, and were validated through western blotting, immunofluorescence and immunohistochemistry. Finally, an orthotopic TNBC mouse model was established and monitored in real time by multimodal ultrasound imaging. The results revealed that nintedanib significantly inhibited TNBC cell proliferation and suppressed stem cell‑like properties. Furthermore, it induced cell cycle arrest at the G₂/M phase and promoted apoptosis. Mechanistic analysis revealed that nintedanib activated tumor protein p73 (TP73), leading to the disruption of the p53‑peroxisome proliferator‑activated receptor α (PPARα)/PI3K‑Akt signaling axis. Additionally, it downregulated epithelial‑mesenchymal transition (EMT) markers, including Snail and zinc finger E‑box‑binding homeobox protein 1, thereby mitigating tumor invasiveness. In vivo, nintedanib treatment effectively reduced tumor growth, angiogenesis and stiffness, indicating its potential as a viable therapeutic agent for TNBC. In conclusion, nintedanib exerts potent anti‑TNBC effects by modulating TP73, disrupting oncogenic signaling via the p53‑PPARα/PI3K‑Akt axis, and attenuating EMT‑associated transcription factors. These findings highlight its potential as a promising targeted therapy for TNBC, warranting further clinical exploration.

Following the publication of the above article, the authors drew to the Editor's attention that the image in Fig. 3A on p. 1356 for the 'Migration/BxPC3/sh‑EGFP' experiment was mistakenly presented. This error arose as a consequence of a mistake that was made during the preparation of the final images. Furthermore, upon performing an independent analysis of the data in this paper in the Editorial Office, it came to light that, for the colony‑formation assay experiments shown in Fig. 2F on p. 1355, the image selected for the 'PaTu8988/Flag‑Furin' experiment had already appeared in a different context in another paper published by the same authors, also in the journal International Journal of Oncology. After having examined their original data, the authors realize that this second figure in the paper had also been inadvertently assembled incorrectly. The revised versions of Fig. 2 (now showing the data correctly for the for the 'PaTu8988/Flag‑Furin' experiment) and Fig. 3 (showing the correct data for the 'Migration/BxPC3/sh‑EGFP' experiment) are shown on the next two pages. Note that the errors made during the compilation of these figures did not affect the overall results and conclusions reported in the paper. The authors are grateful to the Editor of International Journal of Oncology for granting them the opportunity to publish this corrigendum, and all the authors agree with its publication; furthermore, they apologize to the readership of the journal for any inconvenience caused. [International Journal of Oncology 50: 1352‑1362, 2017; DOI: 10.3892/ijo.2017.3896].

Lipoprotein‑associated phospholipase A2 (Lp‑PLA2), an important member of the phospholipase A2 superfamily, was originally investigated for its proinflammatory role in cardiovascular diseases. Recent studies have revealed its significant role in tumorigenesis: It can act as either a tumor promoter or a tumor suppressor depending on the context. The present review systematically outlined the dual mechanisms by which Lp‑PLA2 contributes to cancer pathogenesis. As a tumor promoter, it promotes cancer progression via the induction of epithelial‑mesenchymal transition, glutathione peroxidase 4‑mediated resistance to ferroptosis, and vascular endothelial growth factor‑-dependent angiogenesis; conversely, as a tumor suppressor, it inhibits tumor growth by suppressing the Wnt/β‑catenin pathway in breast cancer gene 1‑mutated cancers or by promoting apoptosis. Mechanistic investigations clarify the interactions between Lp‑PLA2 and critical oncogenic pathways, such as the Notch and HIF1α pathways, while emphasizing the functional dichotomy that is influenced by the microenvironment. Current evidence supports the development of microenvironment‑guided targeting strategies and the potential value of Lp‑PLA2 as a prognostic biomarker and therapeutic target. These findings contribute to a theoretical framework for comprehending the context‑dependent roles of Lp‑PLA2 and may guide the development of innovative therapeutic approaches.

Epithelial‑mesenchymal transition (EMT) is implicated in tumor progression and EMT‑inducing transcription factors play multifaceted roles; however, the molecular mechanisms underlying these processes are not well understood. Previously, we showed that ZEB2 acts cooperatively with the transcription factor SP1 to function as a transcriptional activator that promotes cancer cell invasion and survival, as well as angiogenesis. The present study reported a novel role for Zinc Finger E‑Box Binding Homeobox 2 (ZEB2) in conferring immunosuppressive activity on cancer cells, as well as the underlying molecular mechanism. ZEB2 cooperated with SP1 to upregulate transcription of CD274 and CCL2 by interacting with the proximal SP1 element in their promoters. ZEB2‑mediated programmed cell death 1 ligand 1 (PD‑L1) upregulation on tumor cells inhibited T cell activation and cytokine secretion in a co‑culture system. ZEB2 upregulated C‑C motif chemokine ligand 2 (CCL2) secretion to promote migration of macrophages and drive polarization to an M2‑like phenotype. ZEB2 suppressed the activity of tumor‑infiltrating T cells in a syngeneic mouse tumor model. Furthermore, SUMOylation of ZEB2 by PC2 was required for efficient cooperation between ZEB2 and SP1, as well as for subsequent gene expression. Clinical data showed that ZEB2 expression is associated positively with expression of CD274 and CCL2. Expression of both ZEB2 and CD274 or CBX4 has prognostic significance for predicting survival of colon cancer patients. The present study demonstrated a previously unrecognized role for ZEB2: Direct modulation of the interaction between tumor cells and immune cells. Taken together, the data increased our understanding of the molecular mechanism underlying immunosuppression mediated by an EMT‑inducing transcription factor.