Discover Oncology
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2025
·Vol. 16
·期 1
·1-13
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IF 2.9
Liu Guo,Fang Yu,Li Jiamiao,Chen Zhaofei
Osteosarcoma, the most common primary bone malignancy, poses significant management challenges due to its aggressiveness and metastatic potential. This study investigates the role of anoikis-related genes, particularly phospholipase C beta 4 (PLCB4), as a prognostic biomarker in osteosarcoma. We analyzed transcriptome data from the TARGET and GSE21257 cohorts using bioinformatics tools, identifying 15 significant genes, with PLCB4 as a key marker linked to decreased survival. Our findings indicate a negative correlation between PLCB4 and immune microenvironment scores and checkpoint molecules, suggesting its impact on immunotherapy responses. Drug sensitivity analyses revealed that high PLCB4 expression correlates with lower IC50 values for several chemotherapeutic agents. In vitro experiments showed that silencing PLCB4 inhibited cell proliferation and reduced PD-L1 expression. This study underscores the critical role of PLCB4 in osteosarcoma progression and its potential as a therapeutic target, offering insights into the molecular mechanisms of osteosarcoma biology and improving prognostic accuracy and treatment strategies.
研究领域:
肿瘤学
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分子生物学
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免疫学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2012
·Vol. 13
·期 5
·5818-5831
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IF 2.598
Kun Liu,Feng Liu,Nannan Zhang,Shiying Liu,Yuyang Jiang
Pokemon is an important proto-oncogene that plays a critical role in cellular oncogenic transformation and tumorigenesis. Anoikis, which is regulated by Bim-mediated apoptosis, is critical to cancer cell invasion and metastasis. We investigated the role of Pokemon in anoikis, and our results show that Pokemon renders liver cells resistant to anoikis via suppression of Bim transcription. We knocked-down Pokemon in human hepatoma cells QGY7703 with small interfering RNAs (siRNA). Knockdown of Pokemon alone did not significantly affect the growth and survival of QGY7703 cells but notably enhanced their sensitivity to apoptotic stress due to the presence of chemical agents or cell detachment, thereby inducing anoikis, as evidenced by flow cytometry and caspase-3 activity assays. In contrast, ectopic expression of Pokemon in HL7702 cells led to resistance to anoikis. Dual-luciferase reporter and ChIP assays illustrated that Pokemon suppressed Bim transcription via direct binding to its promoter. Our results suggest that Pokemon prevents anoikis through the suppression of Bim expression, which facilitates tumor cell invasion and metastasis. This Pokemon-Bim pathway may be an effective target for therapeutic intervention for cancer.Keywords:Pokemon;anoikis;Bim;hepatoma
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2026
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IF 12.6
Shengjie Sun,Simin Wen,Ruiqi Zhang,Yanan Fu,Huisong Hao,You Li,Yingfei Wen,Ying Huo,Yixuan Fang,Shihao Zhuang,Jia Tang,Yanglong Hou,Tianqi Wang,Meiying Wu
Cancer-associated fibroblasts (CAFs) are the primary source of collagen I, which contributes to the formation of a dense tumor extracellular matrix (ECM). Non-selective targeting of collagen I through CAF inhibition may inadvertently promote tumor cell detachment and metastasis by triggering anoikis resistance. To address this, a “wandering tumor cells” strategy is proposed, combining the induction of tumor cell deadhesion with the reversal of anoikis resistance. For heterologous targeted drug delivery, thermosensitive lipids and a photosensitizer are incorporated into M1-type macrophage membranes (TMs) to enable laser-responsive activation. Based on this approach, we designed a photothermally triggered, functional macrophage membrane-camouflaged nano-cracker (TM@cP/siF-ErN) with a particle size of 162.20 ± 0.54 nm for the co-delivery of erianin (Er) and focal adhesion kinase small interfering RNA (siFAK). Er is encapsulated in anisamide (AA)-modified nanodiscs (ErN) with hydrodynamic diameter of 15.07 ± 7.24 nm to selectively inhibit collagen I synthesis in CAFs by targeting pyruvate carboxylase, thereby inducing tumor cell deadhesion. siFAK is delivered to tumor cells using cinnamaldehyde-modified polyethyleneimine (cP/siF) to formed complexes with a particle size of 98.57 ± 1.47 nm and enhance transfection efficiency, enabling effective FAK knockdown and reversal of tumor anoikis resistance. Furthermore, TMs are fragmented into debris to amplify M2-type macrophage repolarization. Experimental results show that the nano-cracker efficiently targets orthotopic 4T1 breast tumors and, upon laser-triggered detonation, releases ErN, cP/siF and M1-type macrophage membrane fragments, which collectively promote tumor apoptosis by suppressing collagen I synthesis in CAFs and reversing tumor cell anoikis resistance. Moreover, it promotes the repolarization of M2-type macrophages, which synergizes with collagen I downregulation-induced infiltration of CD8⁺ T lymphocytes to enhance the antitumor immune response, collectively resulting in pronounced breast cancer suppression. This nano-cracker implements the “wandering tumor cells” strategy, offering a promising approach for improving tumor therapy and enabling heterologous targeted delivery.
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高影响因子
Food Science and Human Wellness
·
2024
·
IF 5.6
Ruijie Xu,Zhijie Yao,Hao Zhang,Haitao Li,Wei Chen
Loss of susceptibility to anoikis signals is a crucial step in metastasis. Anoikis resistance therefore represents a promising adjuvant therapeutic target for cancer management. In this study, we have conducted a rationalized screening to search for novel leading anoikis sensitizer from daily foods. Among 19 tested dietary phytochemicals, the best results were obtained with apigenin, a natural component of celery. Phenotypically, apigenin sensitized breast cancer cells to anoikis, lowered the number of circulating tumor cells, and protected against breast cancer metastasis to lung in mice. Mechanistically, we demonstrated that the thromboxane A 2 (TXA 2 )-TXA 2 receptor (TP) axis has a critical role in acquired anoikis resistance by activating PI3K-Akt signaling pathway. Blockage of TXA 2 signaling up-regulated p53 as well as its target gene p21, caused a G1 phase arrest, and finally led to apoptosis in breast cancer cells. TXA 2 level was positively correlated with breast cancer cell anoikis rate, and apigenin significantly inhibited TXA 2 biosynthesis in vitro and in vivo. Collectively, we identified apigenin as a potent anoikis sensitizer with anti-metastatic properties in a mouse model of breast cancer, and these findings might provide a rationale for introducing apigenin supplementation to breast cancer patients.
研究领域:
肿瘤学
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药理学
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分子生物学
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DOI
高影响因子
Translational Oncology
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2025
·
IF 4.1
Ying Shi,Hongda An,Wenshuang Wang,Dong Nan,Yingzhe Cui,Mingyuan He,Jianxiu Lian,Xiaoxiao Zhang,Jing Peng,Xiuhua Yang,Pengfei Liu
Purpose Glioblastoma (GBM), an extremely lethal and aggressive cancer with a poor prognosis and limited therapeutic outcomes, exhibits strong resistance to standard therapies owing to anoikis resistance indicating the need for novel treatments. In this study, we used thermoradiotherapy as an integrative approach for GBM to sensitize its resistance to anoikis. Experimental Design The therapeutic effects of thermoradiotherapy were assessed using cell counting kit-8, colony formation, Transwell, and anoikis assays. Proteomic analysis was performed to identify potential therapeutic targets for thermoradiotherapy. The impact of certain therapeutic target on GBM proliferation, metastasis, and anoikis was identified using EdU, colony formation, Transwell, and anoikis assays. Western blotting and qRT-PCR were used to explore the relevant molecular mechanisms. Results Thermoradiotherapy inhibited proliferation and metastasis of GBM, and reverses anoikis resistance to improve therapeutic outcomes. Proteomic analysis revealed ITGA5 as a prospective therapeutic target. In vitro and in vivo studies identified that ITGA5 promoted GBM proliferation, metastasis, and anoikis resistance by regulating PI3K/AKT pathway activation. Conclusions This study presents a novel thermoradiotherapy for GBM, integrating potent antitumour efficacy and negligible side effects. ITGA5 is a underlying therapeutic target for thermoradiotherapy which related to proliferation, metastasis, and anoikis resistance of GBM.
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Bio-Design and Manufacturing
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2026
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IF 7.9
Wang Yan,Wu Jin,Li Shicheng,Fan Rencai,Li Mingjun,Liu Xin,Yuan Cheng-song,Chang Yuanyuan,Ma Zequn,Guo Chunxian,Li Chang Ming,Chen Bo
Anoikis presents an alternative scheme for suppressing tumor metastasis. While limited by off-target effects, rapid degradation, and reactive oxygen species (ROS) accumulation, anoikis resistance remains a persistent challenge for current tumor therapy. The use of external and endogenous stimuli to trigger ROS bursts, as well as chirality-enhanced tumor microenvironment (TME) penetration, offers a valid solution. We developed a stimuli-responsive nanoreactor by coupling chiral histidine-modified manganese ferrite (MnFe 2 O 4 -PEG) nanoparticles with chiral cysteine-modified black phosphorus (BP) nanosheets via an ROS-sensitive thioketal (TK) bond to form a MnFe 2 O 4 -BP chiral magnetic nanoreactor (CT-MFBP). L-MFBP exhibited superior cellular uptake and intracellular retention due to its enhanced affinity for cell membranes. After entering the TME, the thioketal bond was cleaved by alternating magnetic field (AMF)-induced ROS, leading to the decomposition of the nanoreactor into chiral BP components. Subsequently, ROS accumulation was further amplified using BP-mediated photodynamic therapy (PDT). In addition, the nanoreactor demonstrated catalase (CAT)-like activity, converting endogenous H 2 O 2 into O 2 , thereby effectively alleviating the tumor hypoxic microenvironment and enhancing PDT efficacy. Furthermore, these events activated the mitogen-activated protein kinase (MAPK)-caspase 3 signaling pathway by upregulating p38 protein and Bcl-2-modifying factor (BMF) expression, which together promoted anoikis in tumor cells—a finding further validated by genomic analysis. Both in vitro and in vivo results confirmed that L-MFBP provides a robust regulatory strategy to induce anoikis and suppress tumor metastasis, offering a promising approach for chiral magnetic nanomedicine in clinical antitumor applications.
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-19
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IF 10.6
Liu Yang,Ding Lei,Chen Gaojie,Wang Peiyuan,Wang Xinghuan
Tumor cells can survive when detached from the extracellular matrix (ECM) or lose cell–cell connections, a phenomenon known as anoikis-resistance (AR). AR is closely associated with tumor cell metastasis and recurrence, enabling tumor cells to disseminate, migrate, and invade after detachment. To address this issue, a novel intervention method combining intraoperative hemostasis with multifunctional nanozyme driven-enhanced chemodynamic therapy (ECDT) has been proposed, which holds the potential to weaken the AR capability of tumor cells and suppress tumor recurrence. Here, a nanocomposite containing a dendritic mesoporous nanoframework with Cu 2+ was developed using an anion-assisted approach after surface PEG grafting and glucose oxidase (GOx) anchoring (DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG was further encapsulated in a thermal-sensitive hydrogel (H@DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG utilizes its high peroxidase (POD) activity to elevate intracellular ROS levels, thereby weakening the AR capability of bladder cancer cells. Additionally, through its excellent catalase (CAT) activity, DMSN-Cu@GOx/PEG converts the high level of hydrogen peroxide (H 2 O 2 ) catalyzed by intracellular GOx into oxygen (O 2 ), effectively alleviating tumor hypoxia, downregulating hypoxia-inducible factor-1α (HIF-1α) expression, inhibiting epithelial-mesenchymal transition (EMT) processes, and ultimately suppressing the migration and invasion of bladder cancer cells. Interestingly, in vivo results showed that the thermosensitive hydrogel H@DMSN-Cu@GOx/PEG could rapidly gel at body temperature, forming a gel film on wounds to eliminate residual tumor tissue after tumor resection surgery. Importantly, H@DMSN-Cu@GOx/PEG exhibited excellent hemostatic capabilities, effectively enhancing tissue coagulation during post-tumor resection surgery and mitigating the risk of cancer cell dissemination and recurrence due to surgical bleeding. Such hydrogels undoubtedly possess strong surgical application. Our developed novel nanosystem and hydrogel can inhibit the AR capability of tumor cells and prevent recurrence post-surgery. This study represents the first report of using dendritic mesoporous silica-based nanoreactors for inhibiting the AR capability of bladder cancer cells and suppressing tumor recurrence post-surgery, providing a new avenue for developing strategies to impede tumor recurrence after surgery. Graphical Abstract
研究领域:
生物医学工程
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纳米技术
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癌症生物学
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材料科学
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PubMed
高影响因子
Nanotechnology Reviews
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2019
·Vol. 8
·期 1
·645-660
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IF 2.759
Yu Miao,Jiawei Lu,Junhui Yin,Changchun Zhou,Yaping Guo,Shumin Zhou
Melanoma is the most lethal dermal tumor, and a high recurrence rate and skin defects are two main serious problems. An antimelanoma material,which effectively inhibits tumor recurrence and possesses excellent biocompatibility, is urgently needed to treat melanoma. In this study, we developed a novel antitumor Yb 3+ [Yb(NO 3 ) 3 ]containing chitosan hydrogel (Yb-CS hydrogel) by dissolving Yb(NO 3 ) 3 and chitosan in acetic acid solution and forming composite hydrogels by a freeze-drying process after adding NaOH to the mixed solution. In vitro studies demonstrated that the Yb 3+ produces effect of inducing cell death in Yb-CS hydrogel. Moreover, we found that the Yb-CS hydrogel inhibited a focal adhesion kinase (FAK)-dependent signaling pathway and induced B-16 cell anoikis. However, the Yb-CS hydrogel was less effective on L929 normal mouse dermal cells. In vivo studies showed that the Yb-CS hydrogel inhibited the recurrence of melanoma in a mouse bare xenograft tumor model. We concluded that the Yb-CS hydrogel could potentially be used in the antimelanoma field, especially in the inhibition of melanoma recurrence.
研究领域:
肿瘤学
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材料科学
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生物医学工程
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DOI
高影响因子
Cell Death & Disease
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2025
·Vol. 16
·期 1
·1-14
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IF 9.6
Zhang Pengchao,Cheng Jian,Liu Zhao,Adeshakin Funmilayo O.,Dai Liujiang,Niu Xiangyun,Zhang Ziyang,Peng Xixia,Li Long,Liu Maoxuan,Yan Dehong,Yang Xiaolu,Wan Xiaochun,Zhang Guizhong
Anoikis resistance, an essential prerequisite for tumor metastasis, is now recognized as a promising target in the fight against tumor progression. However, the detailed mechanisms of anoikis resistance are not fully understood, and drugs targeting anoikis resistance are not currently available. Here we report that NY-ESO-1, a well-known cancer-testis antigen, is linked to a poor prognosis in tumor patients and that it is crucial for anoikis resistance and tumor metastasis. Overexpression of NY-ESO-1 in cancer cells enhanced ERK1/2 activation, which in turn promoted resistance to anoikis, increased colony formation in soft agar, and facilitated lung metastasis in mice. Conversely, NY-ESO-1 knockdown significantly reduced ERK1/2 activity, leading to enhanced anoikis, diminished colony formation, and impaired metastatic potential. Mechanistically, NY-ESO-1 acts as a scaffold protein to recruit the deubiquitinase OTUB1 to PP1α, forming a ternary complex that prevents PP1α from being ubiquitinated. The OTUB1’s deubiquitinase activity, not its ability to suppress E2 enzymes, is necessary for reducing polyubiquitination and improving PP1α stability. Finally, accumulated PP1α proteins significantly activate downstream ERK1/2. Blockade of ERK1/2 or knocking down PP1α antagonized NY-ESO-1-mediated anoikis resistance. These results not only reveal a previously unrecognized mode for deubiquitinase substrate expansion but also highlight the function of NY-ESO-1 in anoikis resistance and suggest NY-ESO-1 as a novel attractive target for preventing tumor metastasis.
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International Journal of Medical Sciences
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2025
·Vol. 22
·期 15
·3839-3853
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IF 3.2
Wen Weijia,Li Jiaying,Yuan Li,Liao Yan,Shao Caixia,Xu Dingze,Jiang Hongye,Liao Yuandong,Liu Pan,Zhang Chunyu,Yao Shuzhong,Wang Wei
Lymph node metastasis (LNM) confers significant treatment failure and adverse clinical outcomes in cervical cancer (CCa). However, large unknown lies in the mechanisms underlying LNM in CCa. In this study, we discovered that PRDX3 is elevated in CCa with LNM and associates with poor prognosis in CCa patients. Moreover, multivariate logistic analysis revealed that PRDX3 is an independent predictor of LNM in CCa. Functional investigations demonstrated that PRDX3 promotes invasion, lymphangiogenesis, and LNM of CCa. Mechanistically, PRDX3 activates NF-κB signaling pathway and upregulates the downstream pro-metastatic molecules VEGF-C and MMP-9 in CCa cells. Furthermore, PRDX3 could inhibit the anoikis of detached CCa cells by reducing the ROS level and hence promote LNM in CCa. Importantly, genetic inhibition of PRDX3 potently slows LNM of CCa. These findings highlight a novel PRDX3-mediated mechanism of LNM in CCa and recognize PRDX3 as a promising predictive marker and target of clinical intervention for LNM in CCa.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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癌症研究
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信号转导
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PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2025
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IF 12.5
Yue Gao,Wenxi Li,Wanting Lu,Fuqiang Tang,Xian Xiao,Yinggang Li,Jiaxing Huang,Zhiqi Liang,Yuqing Wu,Yanwen Li,Qingjian Zou,Liangxue Lai,Yanxian Feng,Song Ang,Min Chen
The regenerative capacity of the central nervous system is extremely limited, posing significant challenges for repairing brain injuries. Human induced pluripotent stem cells (hiPSCs) offer a promising cell source for neural regeneration, but their clinical application is hindered by inefficient neuronal differentiation, and poor post-transplant survival. To overcome these challenges, we prepared electrospun fibrous membranes composed of acetylated glucomannan, gelatin, polycaprolactone, and carbon nanotubes. These scaffolds exhibited anti-inflammatory properties in vitro and in vivo . Their excellent adhesion and support properties mimic the extracellular matrix, facilitating the 3D culture of our previous engineered NILB-hiPSCs in vitro . After loading with doxycycline (differentiation inducer) and cyclosporin A (immunosuppressant), the scaffolds achieved sustained release of these agents, ensuring timely neuronal differentiation and maintaining localized immunosuppression, thereby circumventing the need for high systemic doses. Moreover, the composites improved the survival and differentiation of NILB-hiPSCs, promoting the neural repairment in controlled cortex injury mice. Our study highlights the importance of customized multifunctional biomaterials in stem cell transplantation therapy.
研究领域:
生物材料
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干细胞治疗
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神经组织工程
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药物递送系统
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再生医学
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PubMed
高影响因子
Biomaterials Advances
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2024
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IF 5.5
Tianyu Zhang,Xueyuan Wang,Dongna Wang,Meng Lei,Yixue Hu,Zhimeng Chen,Yuting Li,Yingnan Luo,Liefeng Zhang,Yongqiang Zhu
Triple-negative breast cancer (TNBC) is a highly invasive and metastatic subtype of breast cancer that often recurs after surgery. Herein, we developed a cyclodextrin-based tumor-targeted nano delivery system that incorporated the photosensitizer chlorin e6 (Ce6) and the chemotherapeutic agent lonidamine (LND) to form the R6RGD-CMβCD-se-se-Ce6/LND nanoparticles (RCC/LND NPS). This nanosystem could target cancer cells, avoid lysosomal degradation and further localize within the mitochondria. The RCC/LND NPS had pH and redox-responsive to control the release of Ce6 and LND. Consequently, the nanosystem had a synergistic effect by effectively alleviating hypoxia, enhancing the production of cytotoxic reactive oxygen species (ROS) and amplifying the efficacy of photodynamic therapy (PDT). Furthermore, the RCC/LND NPS + light weakened anoikis resistance, disrupted extracellular matrix (ECM), activated both the intrinsic apoptotic pathway (mitochondrial pathway) and extrinsic apoptotic pathway (receptor death pathway) of anoikis. In addition, the nanosystem showed significant anti-TNBC efficacy in vivo . These findings collectively demonstrated that RCC/LND NPS + light enhanced the anticancer effects, induced anoikis and inhibited tumor cell migration and invasion through a synergistic effect of chemotherapy and PDT. Overall, this study highlighted the promising potential of the RCC/LND NPS + light for the treatment of TNBC.
研究领域:
肿瘤学
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药学
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纳米技术
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癌症生物学
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DOI
PubMed
高影响因子
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