Secreted phosphoprotein 1 (SPP1, also known as osteopontin, OPN) is a multifunctional matricellular glycoprotein that is aberrantly overexpressed in nearly all major human malignancies. It functions as a central signaling hub that drives tumor initiation, sustains cancer stemness, accelerates invasion and metastasis, remodels the tumor microenvironment (TME), and mediates immune evasion. SPP1 exerts its oncogenic effects by binding to integrin family receptors (αvβ3, αvβ5, α5β1) and CD44 variants, thereby activating canonical oncogenic signaling cascades including PI3K/AKT, NF‑κB, MAPK/ERK and Wnt/β‑catenin. Beyond cancer‑cell‑autonomous functions, SPP1 orchestrates a complex immunosuppressive TME by modulating tumor‑associated macrophages, cancer‑associated fibroblasts, myeloid‑derived suppressor cells, regulatory T cells (Tregs) and cytotoxic T‑cell activity. Preclinical studies have validated SPP1 as a promising therapeutic target, with strategies including neutralizing antibodies, RNA aptamers, small‑molecule inhibitors, RNA interference and combination immunotherapy showing potent antitumor efficacy. The present review systematically summarizes the molecular basis of SPP1, its receptor‑mediated signaling, multifaceted regulatory roles in tumor biology, TME remodeling, immune suppression and advances in SPP1‑targeted therapy. Current challenges, emerging concepts and future directions to translate SPP1‑targeted interventions into clinical practice for cancers were further discussed.

Non‑small cell lung cancer (NSCLC) remains a leading cause of cancer‑associated mortality and urgently requires new therapeutic agents. In the present study, phenotypic screening of natural herbal extracts was performed, identifying Disporum cantoniense extract as a selective inhibitor of NSCLC cell viability. Bioactivity‑guided fractionation further revealed that the petroleum ether fraction (DPF) was the major active fraction. DPF suppressed the viability, proliferation, colony formation, migration and invasion of A549 and H1299 cells while exhibiting weaker cytotoxicity toward BEAS‑2B cells. In addition, DPF increased propidium iodide (PI)‑positive cell death and lactate dehydrogenase release in NSCLC cells, indicating that DPF‑induced viability loss was accompanied by membrane‑damaging cytotoxicity. Transcriptomic and network pharmacology analyses indicated significant enrichment of autophagy‑, apoptosis‑, AMPK‑, mTOR‑, and MAPK‑associated pathways. Mechanistically, DPF increased LC3‑II accumulation, promoted green fluorescent protein‑LC3 puncta formation and autophagic flux, and activated the AMPK/mTOR/unc‑51 like autophagy activating kinase 1 and MEK/ERK signaling pathways. DPF also induced apoptosis, as demonstrated by increased Annexin V positivity, elevated cleaved caspase‑3 and Bax expression, reduced Bcl‑2 expression, and reduced cytotoxicity in Bax‑Bak double‑knockout mouse embryonic fibroblast (MEF) cells. Notably, pharmacological inhibition of autophagy or its upstream regulators attenuated DPF‑induced cytotoxicity. In addition, autophagy‑deficient Atg7‑/‑ MEF cells exhibited reduced DPF‑induced PI‑positive cell death, loss of cell viability, and caspase‑3 activation, further supporting the involvement of Atg7‑dependent autophagy in DPF‑induced apoptosis. In a xenograft model, DPF significantly inhibited tumor growth and increased apoptosis‑ and autophagy‑associated markers in tumor tissues without evident systemic toxicity. Collectively, these findings identify DPF as a principal anti‑NSCLC fraction of Disporum cantoniense and suggest that it suppresses NSCLC progression through AMPK/mTOR/unc‑51 like autophagy activating kinase 1‑ and MEK/ERK‑mediated autophagy‑dependent apoptosis.

Following the publication of the above article, an interested reader drew the authors' attention to the fact that, for the western blots shown in Fig. 5 on p. 914, the β‑actin blots shown in the rightmost lanes for the 'BcPc3 OSIR' blots (the 'Crixotinib' and 'Af+Cr' lanes of the gel) were strikingly similar to the β‑actin blots shown in Fig. 2B (for the 'BxPc3 parental' blots), albeit with horizontal and vertical resizing of the bands concerned. Upon contacting the authors, they realized that Fig. 5 had inadvertently been assembled incorrectly (the same β‑actin cropped image was used for both samples in question after the files had erroneously being saved under the same name). The authors were able to consult their original data, and provided the Editorial Office with access to the images of the relevant full‑length original blots. The revised version of Fig. 5, now showing the correct data for the β‑actin blots for the 'BcPc3 OSIR' experiments, is shown on the next page. Note that this error did not affect the overall conclusions reported in the study. The authors are grateful to the Editor of International Journal of Oncology for allowing them this opportunity to publish a Corrigendum, and all the authors agree with its publication. Furthermore, the authors thank the interested reader for drawing this error in their paper to their attention, and apologize to the readership for any inconvenience caused. [International Journal of Oncology 48: 908‑918, 2016; DOI: 10.3892/ijo.2016.3320].

P‑element induced wimpy testis (PIWI)‑interacting RNAs (piRNAs) are small non‑coding RNAs with a length of ~24‑32 nucleotides that specifically bind members of the PIWI protein family. Initially identified in germ cells, piRNAs have since been detected in various somatic cells. They regulate multiple physiological and pathological processes and their aberrant expression contributes to human diseases, including cancer. Recent studies indicate that piRNAs influence key tumour behaviours‑including malignant proliferation, invasion and metastasis, angiogenesis, immune evasion and metabolic reprogramming‑through epigenetic, transcriptional and post‑transcriptional mechanisms. In tumour‑bearing mouse models, exogenous knockdown or overexpression of piRNAs using nanodelivery systems can markedly inhibit tumour growth, supporting their potential as therapeutic targets. piRNAs are also stably expressed in tumour tissues and bodily fluids, such as serum and urine, either freely circulating or encapsulated within extracellular vesicles; their dysregulation is associated with clinicopathological features of tumours. Accordingly, piRNAs may serve as novel pathological diagnostic markers or liquid biopsy biomarkers. This review summarises piRNA expression patterns and molecular mechanisms, evaluates their clinical potential in cancer diagnosis and treatment and integrates advances in high‑throughput sequencing and nanodelivery technologies to provide a theoretical basis and research foundation for the clinical translation of piRNA‑related studies.

As a classic cytosolic DNA sensor, the cyclic GMP‑AMP synthase (cGAS)‑stimulator of interferon genes (STING) pathway contributes to the secretion of multiple inflammatory molecules and functions as a suppressor or promoter in tumor development. Currently, the effect of this pathway on digestive tract cancer types remains unclear, which may be due to its paradoxical roles in different cell types. Tumor cells in digestive cancer often employ multiple mechanisms to inhibit this pathway activation, which then restricts the infiltration of antitumor immune cells and facilitates the formation of an immunosuppressive microenvironment. However, cGAS‑STING pathway activation also influences the function of multiple immune cells. For example, while it mainly potentiates the function of dendritic cells and natural killer cells in the tumor microenvironment, it can also promote macrophage polarization into the immunosuppressive M2 subset. To improve the understanding of the cGAS‑STING pathway in digestive cancer types, the present article systematically reviews the regulatory mechanism and effects of this pathway across different malignancies of the digestive system, including oral cavity, esophageal, gastric, hepatobiliary, pancreatic and colorectal cancer. Furthermore, the present review examines potential stimulatory strategies and future directions to utilize this pathway against tumors, such as inducing DNA damage, removing cell‑intrinsic inhibitory signals and direct activation by agonists. Overall, the present review aims to provide new perspectives and ideas for leveraging the cGAS‑STING pathway to exert antitumor effects by highlighting the changes and roles of this pathway in digestive tract cancer types.

B‑cell receptor (BCR) signaling is essential for the survival and proliferation of normal B cells, and contributes substantially to the pathogenesis of diffuse large B‑cell lymphoma (DLBCL). Bruton's tyrosine kinase (BTK), a key downstream component of the BCR pathway, has emerged as an important therapeutic target in B‑cell malignancies. However, the clinical efficacy of BTK inhibitors (BTKi) in DLBCL remains heterogeneous and is strongly influenced by molecular subtype and signaling dependency. Accumulating evidence indicates that BTKi resistance in DLBCL is driven by diverse molecular mechanisms, including BTK mutations, gain‑of‑function alterations in phospholipase Cγ2, activation of the caspase recruitment domain family member 11‑B‑cell lymphoma/leukemia 10‑mucosa‑associated lymphoid tissue lymphoma translocation protein 1 complex and dysregulation of myeloid differentiation primary response 88, cluster of differentiation 79B, tumor necrosis factor‑α‑induced protein 3 and Kelch‑like protein 14. In addition to these genetic determinants, non‑genetic adaptive mechanisms, such as compensatory phosphoinositide 3‑kinase/AKT/mechanistic target of rapamycin and mitogen‑activated protein kinase/extracellular signal‑-regulated kinase signaling, epigenetic reprogramming, tumor microenvironment remodeling, metabolic rewiring and endoplasmic reticulum stress, may further contribute to therapeutic escape. Emerging approaches, including next‑generation covalent and non‑covalent BTKi, dual‑mode inhibitors, BTK‑targeting degraders, allosteric inhibitors and multi‑target strategies, are currently being investigated as potential strategies to address BTKi resistance. The present review summarized the molecular mechanisms underlying BTKi resistance in DLBCL and discussed their potential implications for biomarker development, rational combination therapy and future precision treatment.

Lung adenocarcinoma (LUAD) represents the most prevalent type of lung cancer, accounting for 35‑40% of all lung cancer cases. Regulatory T cells (Tregs), a CD4[+] T cell subtype with immunosuppressive functions, play a pivotal role in maintaining self‑tolerance under physiological conditions. Recent evidence has increasingly highlighted their involvement in various cancers. In LUAD, Treg infiltration into tissues undermines the immune anticancer response, correlating with disease stage, treatment efficacy and prognosis. By inhibiting robust anti‑tumor immune mechanisms, Tregs facilitate tumor immune escape in LUAD. Furthermore, elevated Treg cell accumulation in LUAD has been linked to reduced overall survival rates. Tregs serve as independent predictors for LUAD diagnosis in patients at high risk of recurrence. Systematic depletion of all Tregs to enhance anticancer efficacy poses risks of inducing severe autoimmune pathologies. Consequently, understanding the precise structure of tumor‑infiltrating Tregs is essential for effective targeting of these cells in tumors. Additionally, identifying candidate targets or methods for the specific elimination of tumor‑infiltrating Tregs is necessary for developing efficient and safe combination immunotherapy strategies for LUAD. The present study focuses on the regulatory role of Tregs in LUAD prognosis, immune escape and targeted therapies, elucidating the molecular mechanisms of Treg involvement and presenting associated therapeutic targets.

Proper localization of proteins and RNAs in a cell is crucial for physiological function and cellular homeostasis, while disruption of the nucleocytoplasmic transport machinery leads to carcinogenesis. In gynaecological (endometrial, cervical and ovarian) tumours, upregulated nuclear transport protein expression promotes malignant cell proliferation, invasion and resistance to therapy. Therefore, therapeutic targeting of nuclear transport proteins has emerged as a promising anticancer approach. Researchers have extensively studied both nuclear import and export inhibitors in preclinical settings, alone or in combination with other targeted therapy agents. However, to date, only one compound, the exportin 1 inhibitor Selinexor, has been approved for cancer treatment. The development of nuclear transport inhibition‑based therapies is hindered by limited inhibitor specificity and complex cellular resistance mechanisms. The aim of the present review was to clarify the connection between nuclear transport dysregulation, hallmarks of gynaecological tumours and the challenges of inhibiting nuclear transport in gynaecological cancer treatment.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that the gelatinase zymography data shown in Figs. 6, 10 and 14 on p. 1792, 1794 and 1795 respectively had also been included in a paper written by the same research group which had already been published in the same journal (International Journal of Oncology). Even though these data appeared to have been included in the two papers to show the same experimental details, given the re‑use of these data in the above paper, the authors were requested to submit replacement data for these figures to be included in a corrigendum. Given the 13 years that have elapsed since the publication of these papers, the only available author was unable to verify and comply with this request; therefore, the Editor has decided that this paper should be retracted from the Journal on account of the re‑use of the abovementioned data. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 43: 1787‑1798, 2013; DOI: 10.3892/ijo.2013.2113].

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that the control β‑actin blots shown in Fig. 1D and G on p. 195 appeared to be very similar, albeit with rotation of one set of the blots through 180°, and with resizing of the bands. Similarly, certain of the β‑actin protein bands shown in Fig. 1G were strikingly similar to the control β‑actin protein bands shown in Fig. 5A on p. 200, suggesting that data in these figures had been assembled incorrectly. The authors were contacted by the Editorial Office to offer an explanation for the apparent 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 39: 193‑202, 2011; DOI: 10.3892/ijo.2011.1002].

Membrane associated guanylate kinase WW and PDZ domain containing 3 (MAGI3) functions as a tumor suppressor in lung cancer, but its role and mechanism in non‑small cell lung cancer (NSCLC) progression remain unclear. MAGI3 expression was detected in NSCLC tissues (immunohistochemistry) and cell lines (western blotting). Tet‑on inducible MAGI3 overexpression was used to assess effects on NSCLC cells via Cell Counting Kit‑8, Transwell, colony/sphere formation, β‑Galactosidase staining and flow cytometry. Ubiquitination/half‑life assays analyzed MAGI3‑TAZ (transcriptional co‑activator with PDZ‑binding motif) interaction. In situ and xenograft tumor models evaluated tumor growth and metastasis. The Cancer Genome Atlas data, clinical samples, and cell lines showed downregulated MAGI3 in NSCLC, correlating with poor prognosis. MAGI3 overexpression reduced cell viability, clonogenicity, sphere formation, migration and invasion; induced G1 phase arrest (reduced CyclinD1) and cellular senescence. MAGI3 specifically promoted TAZ ubiquitination via PDZ domain‑mediated interaction, which subsequently blocked β‑catenin nuclear translocation, dampened Wnt signaling components (DVL2/phosphorylated GSK3β), and reduced TCF/LEF transcriptional output. Reconstitution of TAZ reversed MAGI3‑mediated inhibition of Wnt pathway markers (cMYC, c‑JUN, WISP1 and PPARD). In vivo, MAGI3 overexpression suppressed tumor growth and lung metastasis, while MAGI3 silencing increased metastatic nodules. The present study identified that MAGI3, as a suppressor in NSCLC progression, repressed the Wnt pathway‑including TAZ degradation, impaired β‑catenin nuclear translocation, and diminished TCF/LEF transcription‑thereby restraining tumorigenesis and metastasis of NSCLC.

Renal cell carcinoma (RCC) is the main pathological type of kidney cancer, which accounts for approximately 85‑95% of all cases of kidney cancer. Despite the emergence of targeted therapies and immunotherapies, however, the development of resistance remains common. Eomesodermin (Eomes) is a member of the T‑box transcription factor family that links both developmental biology and immune regulation with tumor‑associated programs. In RCC, its function appears to be context‑dependent. In tumor‑infiltrating leukocytes, Eomes has been shown to support mature natural killer cell and memory CD8[+] T‑cell function, whereas persistent or dysregulated Eomes is associated with exhausted CD8[+] T cells and Eomes‑positive type 1 regulatory T‑like immunosuppressive cells. In both intrinsic RCC tumor cells and stromal/endothelial compartments, current knowledge remains relatively limited, and what evidence there is has often been derived from indirect RCC pathway research, other tumor types or developmental models. The present review summarizes Eomes‑associated mechanisms in RCC through distinguishing among infiltrating leukocytes, tumor cells and stromal/endothelial compartments, and also through separating direct RCC evidence from indirectly derived mechanistic inferences. Epigenetic regulation, PI3K/Akt/mTOR signaling, Wnt/β‑catenin signaling, angiogenesis and therapeutic resistance are also discussed according to the strength of the available evidence. Current data support that Eomes stands as an exploratory biomarker and hypothesis‑generating therapeutic node, rather than as an established clinical target. Further research should be performed, however, to validate the cell‑type‑specific functions of Eomes in RCC tissues, single‑cell and spatial datasets, in addition to experimental RCC models.

Following the publication of the above article, and an Expression of Concern statement (doi: 10.3892/ijo.2026.5908) that was published in light of the fact that the GAPDH control western blots shown in Fig. 5A on p. 9 were strikingly similar to the GAPDH control western blots shown in Fig. 5D, the authors have responded to the queries raised by the Editorial Office. The GAPDH panels shown in Figs. 5A and 5D were generated from the same experiment and the same set of protein lysates: Fig. 5A presented the analysis of total protein expression, whereas Fig. 5D presented immunoprecipitation analyses performed using material derived from these same experimental samples. Consequently, the GAPDH loading control was legitimately shared between the two figures. However, given that the original figure legend did not explicitly state that the same GAPDH loading control was used for both analyses, to eliminate any possible ambiguity for readers, the authors have revised Fig. 5 by replacing the representative '-MG132 panel' in Fig. 5A with results obtained from an independent repeat experiment performed under identical experimental conditions. The revised version of Fig. 5 is shown on the next page. Note that this revised figure reproduces the original findings, and does not affect the quantitative analyses, the interpretation of the data, or the conclusions of the study. Regarding a query raised by the Editorial Office concerning the presentation of flow cytometric plots in Fig. 8, the authors explained that Fig. 8E was generated by applying an additional fluorescence gate to the parent flow cytometry dataset shown in Fig. 8B, which represents standard flow cytometric analysis, rather than duplication of experimental data, and so this figure was presented correctly, and as intended by the authors. The authors thank the Editor of International Journal of Oncology for granting them the opportunity to publish this corrigendum, and all the authors agree with its publication. [International Journal of Oncology 59: 89, 2021; DOI: 10.3892/ijo.2021.5269].

Lung cancer is one of the most common and deadly forms of cancer worldwide, with >80% of cases being non‑small cell lung cancer. Its recurrence and drug resistance have been major challenges in clinical treatment, posing a serious threat to the lives of patients. The present study found that high xeroderma pigmentosum group C (XPC) expression markedly reduced the proliferation capacity and stem cell characteristics of the lung cancer cell lines A549‑XPC and H460‑XPC. In addition, XPC overexpression led to a decreased in the proportion of cells in the G2/M phase proportion, suggesting alterations in the cell cycle process. MTS assays showed that XPC overexpressing cells demonstrated markedly higher sensitivity to chemotherapy drugs compared with control cells. Furthermore, the clonogenic and anchorage‑independent spheroid formation capacities of the cells were markedly inhibited with high XPC expression and the phosphorylation levels of the JAK/STAT pathway and the expression levels of stemness‑associated markers were markedly altered. In vivo studies validated the effect of high XPC expression on tumorigenicity using a subcutaneous tumor model, with tumor volumes of 134.04±46.77 mm³ and 324.64±85.31 mm³ and weights of 164.24±76.16 mg and 434.70±115.72 mg for subcutaneously injected A549‑XPC and A549‑CTR cells, respectively. High expression of XPC in the A549 cells significantly affected tumor volume (P<0.05) and weight (P<0.01) in vivo. The present findings suggested that high XPC expression is associated with reduced proliferation, migration and stem cell‑like properties in lung cancer cells, enhances their sensitivity to chemotherapy drugs and suppresses tumor growth in vivo. These observations supported further investigation of XPC as a potential therapeutic target and prognostic marker for lung cancer, offering new strategies to improve treatment outcomes and prolong patient survival.

Dendritic cell (DC)‑based vaccines have emerged as a promising immunotherapy against a broad range of cancers. DCs are sentinel antigen‑presenting cells that play a pivotal role in cancer immunosurveillance by recognizing tumor antigens via innate immune responses and subsequently stimulating adaptive T‑cell‑mediated anti‑tumor responses. Autologous DC‑based vaccines prime the individual's immune system to recognize and destroy tumor cells, aiming to achieve durable anti‑tumor immunity and impede tumor relapse. The safety and effectiveness of DC‑based vaccines for cancer treatment have been demonstrated in several clinical studies, either as monotherapy (such as Sipuleucel‑T) or in combination with other therapies such as chemotherapy and immune checkpoint blockade. The present review provides a comprehensive overview of the current progress and clinical applications of DC‑based vaccines for colorectal cancer (CRC). Various subsets of DCs and their biological roles in anti‑tumor immunity are explored in detail and the mechanistic insights into DC‑based vaccine development are discussed. Additionally, the present review highlighted the outcomes of recent clinical trials of autologous DC‑based vaccines for advanced CRC, as well as the challenges and strategies for overcoming them in the development and clinical applications for CRC. Taken together, the potential and limitations of DC‑based vaccines for CRC are underscored in the present review to provide an improved understanding and guide future directions in developing efficacious DC‑based therapeutic vaccines for CRC.