Cancer Science最新文献

AmNA-Modified Antisense Oligonucleotide Targeting MCM8 as a Cancer-Specific Chemosensitizer for Platinum Compounds 靶向MCM8的amna修饰反义寡核苷酸作为铂类化合物的癌症特异性化学增敏剂。

IF 4.5 2区医学

Cancer Science Pub Date : 2025-03-17 DOI: 10.1111/cas.70024

Yuki Uchibori, Masaki Suekuni, Yuko Kokaji, Kazumasa Yoshida, Tohru Kiyono, Yuuya Kasahara, Masatoshi Fujita

{"title":"AmNA-Modified Antisense Oligonucleotide Targeting MCM8 as a Cancer-Specific Chemosensitizer for Platinum Compounds","authors":"Yuki Uchibori, Masaki Suekuni, Yuko Kokaji, Kazumasa Yoshida, Tohru Kiyono, Yuuya Kasahara, Masatoshi Fujita","doi":"10.1111/cas.70024","DOIUrl":"10.1111/cas.70024","url":null,"abstract":"MCM8 and MCM9 participate in homologous recombination with long-tract gene conversion to repair double-strand breaks caused by replication stress, which is generally higher in cancer cells than in normal cells. MCM8 is highly expressed in certain cancer cells, where it is necessary for maintaining cell growth, migration, and invasion, although the molecular mechanisms remain unclear. Knockdown with siRNAs or knockout of MCM8 or MCM9 selectively sensitizes cancer cells to cisplatin. Thus, drugs inhibiting MCM8 or MCM9 could serve as novel anti-neoplastic agents and/or chemosensitizers that selectively sensitize cancer cells to platinum compounds. The present study describes the development of an amido-bridged nucleic acid (AmNA)-modified gapmer antisense oligonucleotide (ASO) targeting MCM8, called ASO 8–3419. In vitro, ASO 8–3419 inhibited MCM8 expression in several human cell lines and selectively sensitized cancer cells to cisplatin. Moreover, ASO 8–3419 modestly suppressed the growth of several cancer cell lines whose proliferation has been reported to depend on MCM8. In vivo, ASO 8–3419 inhibited the expression of MCM8 in xenografted tumors of colon cancer-derived HCT116 cells in nude mice and increased tumor sensitivity to cisplatin with minimal toxicity. These findings suggest that AmNA-modified, MCM8-specific ASOs hold promise as novel anti-cancer agents.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 5","pages":"1405-1416"},"PeriodicalIF":4.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LncRNA-DANCR Promotes ESCC Progression and Function as ceRNA to Regulate DDIT3 Expression by Sponging microRNA-3193 LncRNA-DANCR通过海绵microRNA-3193促进ESCC进展并作为ceRNA调节DDIT3表达的功能。

IF 4.5 2区医学

Cancer Science Pub Date : 2025-03-12 DOI: 10.1111/cas.70035

Heng Xiao, Tong Zhou, Yanfang Yang, Xin Yang, Yanghui Bi, Xiaolong Cheng

引用次数: 0

Impact of Minimal Residual Disease on Early Recurrence of Liver Metastatic Colorectal Cancer 微小残留病变对肝转移性结直肠癌早期复发的影响。

IF 4.5 2区医学

Cancer Science Pub Date : 2025-03-10 DOI: 10.1111/cas.16442

Mampei Kawashima, Takeshi Yamada, Toshimitsu Miyasaka, Shintaro Kanaka, Sho Kuriyama, Kay Uehara, Akihisa Matsuda, Ryo Ohta, Hiromichi Sonoda, Nobuhiko Taniai, Hiroshi Yoshida

{"title":"Impact of Minimal Residual Disease on Early Recurrence of Liver Metastatic Colorectal Cancer","authors":"Mampei Kawashima, Takeshi Yamada, Toshimitsu Miyasaka, Shintaro Kanaka, Sho Kuriyama, Kay Uehara, Akihisa Matsuda, Ryo Ohta, Hiromichi Sonoda, Nobuhiko Taniai, Hiroshi Yoshida","doi":"10.1111/cas.16442","DOIUrl":"10.1111/cas.16442","url":null,"abstract":"For patients with resectable colorectal liver metastases (CRLM), the efficacy of adjuvant chemotherapy remains a subject of debate. Several studies have concluded that postoperative circulating tumor DNA (ctDNA) is a marker of minimal residual disease (MRD) and is a useful prognostic factor in patients with nonmetastatic colorectal cancer. However, few studies have explored its application in cases involving metastases. This was an observational study that included CRLM patients who underwent primary and liver tumor resection. By examining targeted sequencing of 50 genes commonly mutated in CRC, we identified at least one somatic mutation in each patient's metastatic liver tumor. Blood samples were obtained before and 1-month after surgery. Fifty-three patients were included, and recurrence was diagnosed in 39 patients. Of those, 13 patients experienced early relapse. ctDNA was detected in 45 patients before surgery and 11 after. All MRD-positive patients experienced recurrence. Among them, nine had early recurrence. MRD-positive patients had poorer recurrence free survival (RFS, p < 0.0001) and overall survival (OS, p < 0.0005). Nine of 13 patients with early recurrence had MRD; however, two of 40 patients without early recurrence also had MRD (p < 0.0001). Among 42 MRD-negative patients, adjuvant chemotherapy had no impact of RFS (p = 0.84) or OS (p = 0.54). MRD proved valuable in predicting the risk of postoperative recurrence in patients with CRLM, particularly because MRD positivity emerged as a significant risk factor for early recurrence. Furthermore, it appears that adjuvant chemotherapy may not effectively improve the prognosis for MRD-negative patients.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 5","pages":"1366-1374"},"PeriodicalIF":4.5,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.16442","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel Approach to Overcome Osimertinib Resistance Using Bromodomain and Extra-Terminal Domain Inhibitors 利用溴域和超末端结构域抑制剂克服奥西替尼耐药性的新方法。

IF 4.5 2区医学

Cancer Science Pub Date : 2025-03-04 DOI: 10.1111/cas.70032

Yosuke Miyashita, Ken Tajima, Kenta Izumi, Naohisa Matsumoto, Daisuke Hayakawa, Ikuko Takeda Nakamura, Isana Katayama, Adityo Wibowo, Hironari Matsuda, Wira Winardi, Bagus Radityo Amien, Yoichiro Mitsuishi, Fumiyuki Takahashi, Kohta Nakamura, Ken Uchibori, Noriko Yanagitani, Takuo Hayashi, Kazuya Takamochi, Kenji Suzuki, Ryohei Katayama, Kazuhisa Takahashi

{"title":"Novel Approach to Overcome Osimertinib Resistance Using Bromodomain and Extra-Terminal Domain Inhibitors","authors":"Yosuke Miyashita, Ken Tajima, Kenta Izumi, Naohisa Matsumoto, Daisuke Hayakawa, Ikuko Takeda Nakamura, Isana Katayama, Adityo Wibowo, Hironari Matsuda, Wira Winardi, Bagus Radityo Amien, Yoichiro Mitsuishi, Fumiyuki Takahashi, Kohta Nakamura, Ken Uchibori, Noriko Yanagitani, Takuo Hayashi, Kazuya Takamochi, Kenji Suzuki, Ryohei Katayama, Kazuhisa Takahashi","doi":"10.1111/cas.70032","DOIUrl":"10.1111/cas.70032","url":null,"abstract":"Osimertinib, a third-generation EGFR-tyrosine kinase inhibitor, is the first-line therapy for lung cancer harboring EGFR mutations. The mechanisms underlying osimertinib resistance are diverse, with approximately half remaining unknown. Epigenetic dysregulation is implicated in drug resistance; however, the mechanisms remain unclear. Therefore, we investigated epigenetic involvement in osimertinib resistance and its therapeutic potential. We established osimertinib-resistant cells and used an assay for transposase-accessible chromatin using sequencing to evaluate chromatin accessibility, finding significant changes post-resistance. Combining the assay for transposase-accessible chromatin and RNA sequencing data, we identified FGF1 as a resistance-related gene regulated by histone modifications. FGF1 induced osimertinib resistance, and its suppression attenuated resistance. Bromodomain and extra-terminal domain inhibitors combined with osimertinib overcame osimertinib resistance by reducing FGF1 expression. Increased FGF1 expression was observed in osimertinib-resistant clinical samples. This combination therapy was effective in cell lines and mouse xenograft models. These results suggest targeting histone modifications using bromodomain and extra-terminal domain inhibitors as a novel approach to overcoming osimertinib resistance.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 5","pages":"1392-1404"},"PeriodicalIF":4.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Feasibility of Intratumoral Administration With EPHB4-CAR-T Cells for the Treatment of Oral Squamous Cell Carcinoma 肿瘤内注射EPHB4-CAR-T细胞治疗口腔鳞状细胞癌的可行性

IF 4.5 2区医学

Cancer Science Pub Date : 2025-03-03 DOI: 10.1111/cas.70023

Yusuke Ito, Toshihiro Suzuki, Manami Shimomura, Kazumasa Takenouchi, Kazunobu Ohnuki, Kayoko Shoda, Yuka Kenmochi, Shigeki Yagyu, Kazuto Matsuura, Ryuichi Hayashi, Tetsuya Nakatsura

{"title":"Feasibility of Intratumoral Administration With EPHB4-CAR-T Cells for the Treatment of Oral Squamous Cell Carcinoma","authors":"Yusuke Ito, Toshihiro Suzuki, Manami Shimomura, Kazumasa Takenouchi, Kazunobu Ohnuki, Kayoko Shoda, Yuka Kenmochi, Shigeki Yagyu, Kazuto Matsuura, Ryuichi Hayashi, Tetsuya Nakatsura","doi":"10.1111/cas.70023","DOIUrl":"10.1111/cas.70023","url":null,"abstract":"Oral squamous cell carcinoma (OSCC) represents the most common type of oral cancer, and its prognosis remains poor. In this study, we found that almost OSCC cases showed high Ephrin type-B receptor 4 (EPHB4) expression that was mainly localized on the membrane of tumor cells. Therefore, EPHB4 represents a potential target of chimeric antigen receptor (CAR) T cell therapy for OSCC treatment. Because the oral cavity can be directly accessed, local administration of CAR-T cells is feasible for treating OSCC. In this study, we investigated the efficacy of intratumoral injection of EPHB4-specific CAR-T cells in OSCC using xenograft models. To evaluate the anti-tumor effect, the SAS OSCC cell line or an OSCC patient-derived xenograft (PDX) tumor was subcutaneously implanted into NOD SCID gamma mice, and EPHB4-CAR-T cells were intratumorally injected twice. As expected, administration of CAR-T cells suppressed tumor growth of both SAS cells and PDX tumor. EPHB4 expression in tumor tissues was attenuated by CAR-T cell treatment, which was accompanied by a reduction in tumor area and accumulation of CAR-T cells. Our findings suggest that intratumoral injection of EPHB4-CAR-T cells represents a potential therapeutic strategy for OSCC.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 5","pages":"1227-1238"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transferrin Receptor Promotes Endometrial Cancer Proliferation by Activating the Iron-Dependent PI3K/AKT/mTOR Signaling Pathway 转铁蛋白受体通过激活铁依赖性 PI3K/AKT/mTOR 信号通路促进子宫内膜癌增殖

IF 4.5 2区医学

Cancer Science Pub Date : 2025-03-01 DOI: 10.1111/cas.70015

Yufei Yang, Ying Ning, Yu Chen, Tian Tian, Xinyan Gao, Yan Kong, Ke Lei, Zhumei Cui

{"title":"Transferrin Receptor Promotes Endometrial Cancer Proliferation by Activating the Iron-Dependent PI3K/AKT/mTOR Signaling Pathway","authors":"Yufei Yang, Ying Ning, Yu Chen, Tian Tian, Xinyan Gao, Yan Kong, Ke Lei, Zhumei Cui","doi":"10.1111/cas.70015","DOIUrl":"10.1111/cas.70015","url":null,"abstract":"Aberrant iron metabolism is frequently observed in cancers, including endometrial cancer (EC). However, the role of transferrin receptor (TFRC), a key regulator of iron metabolism, remains unclear in endometrial cancer. We found transferrin receptor expression was significantly upregulated in endometrial cancer tissues compared to adjacent nontumor tissues, and high transferrin receptor levels were associated with poor prognosis. Functional studies revealed that transferrin receptor knockdown impaired endometrial cancer cell proliferation in vitro and in vivo, while transferrin receptor overexpression enhanced endometrial cancer cell proliferation. Mechanistically, transferrin receptor activated the PI3K/AKT/mTOR signaling pathway, as its knockdown suppressed the pathway, and rapamycin, an mTOR inhibitor, reversed transferrin receptor-induced pathway activation and proliferation. Modulation of the labile iron pool by ferric ammonium citrate (FAC) or deferoxamine (DFO) rescued transferrin receptor-induced biological effects. Additionally, AURKA was identified as a regulator of transferrin receptor expression. These findings demonstrate the oncogenic role of transferrin receptor in endometrial cancer and suggest that targeting iron homeostasis and the PI3K/AKT/mTOR pathway may represent potential therapeutic strategies for endometrial cancer.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 5","pages":"1352-1365"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Insights From Nonsense-Mediated mRNA Decay for Prognosis in Homologous Recombination-Deficient Ovarian Cancer 从无义基因介导的 mRNA 衰变洞察同源重组缺陷卵巢癌的预后

IF 4.5 2区医学

Cancer Science Pub Date : 2025-03-01 DOI: 10.1111/cas.70034

Lei Han, Jialing Liu, Runjiao Zhang, Yanan Cheng, Li Dong, Lijuan Wei, Juntian Liu, Ke Wang, Jinpu Yu

{"title":"Insights From Nonsense-Mediated mRNA Decay for Prognosis in Homologous Recombination-Deficient Ovarian Cancer","authors":"Lei Han, Jialing Liu, Runjiao Zhang, Yanan Cheng, Li Dong, Lijuan Wei, Juntian Liu, Ke Wang, Jinpu Yu","doi":"10.1111/cas.70034","DOIUrl":"10.1111/cas.70034","url":null,"abstract":"Not all ovarian cancer patients with homologous recombination deficiency, especially those with germline BRCA mutations, can benefit from platinum-based and targeted therapy. Our study aimed to determine the value of nonsense-mediated mRNA decay, which targeted these mutations. The retrospective analysis of 797 ovarian cancer patients was performed using two public cohorts and one in-house cohort. We developed a prediction algorithm for nonsense-mediated mRNA decay to discriminate between trigger and escape status, finding that escape status indicated a better prognosis. Subsequently, we analyzed differential gene expression and functional pathways between the two statuses and filtered 8 genes associated with the cell cycle. Then the optimized key gene model was built using integrated machine learning algorithms (mean AUC > 0.89), which had a higher independent prognostic value for ovarian cancer with germline BRCA variants or homologous recombination deficiency than the nonsense-mediated mRNA decay algorithm. Furthermore, we classified patients into high- and low-risk groups by the machine learning model and found that the low-risk group had a better prognosis with higher drug response and immune levels of activated dendritic cells than the high-risk controls. Our findings provide a perspective based on nonsense-mediated mRNA decay and cell cycle pathways to distinguish subtypes of germline BRCA or homologous recombination deficiency.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 5","pages":"1449-1463"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High Antigenicity for Treg Cells Confers Resistance to PD-1 Blockade Therapy via High PD-1 Expression in Treg Cells Treg细胞的高抗原性通过在Treg细胞中高PD-1表达赋予PD-1阻断治疗抗性。

IF 4.5 2区医学

Cancer Science Pub Date : 2025-02-27 DOI: 10.1111/cas.70029

Hiroaki Matsuura, Takamasa Ishino, Toshifumi Ninomiya, Kiichiro Ninomiya, Kota Tachibana, Akiko Honobe-Tabuchi, Yoshinori Muto, Takashi Inozume, Youki Ueda, Kadoaki Ohashi, Yoshinobu Maeda, Joji Nagasaki, Yosuke Togashi

{"title":"High Antigenicity for Treg Cells Confers Resistance to PD-1 Blockade Therapy via High PD-1 Expression in Treg Cells","authors":"Hiroaki Matsuura, Takamasa Ishino, Toshifumi Ninomiya, Kiichiro Ninomiya, Kota Tachibana, Akiko Honobe-Tabuchi, Yoshinori Muto, Takashi Inozume, Youki Ueda, Kadoaki Ohashi, Yoshinobu Maeda, Joji Nagasaki, Yosuke Togashi","doi":"10.1111/cas.70029","DOIUrl":"10.1111/cas.70029","url":null,"abstract":"Regulatory T (Treg) cells have an immunosuppressive function, and programmed death-1 (PD-1)-expressing Treg cells reportedly induce resistance to PD-1 blockade therapies through their reactivation. However, the effects of antigenicity on PD-1 expression in Treg cells and the resistance to PD-1 blockade therapy remain unclear. Here, we show that Treg cells gain high PD-1 expression through an antigen with high antigenicity. Additionally, tumors with high antigenicity for Treg cells were resistant to PD-1 blockade in vivo due to PD-1+ Treg-cell infiltration. Because such PD-1+ Treg cells have high cytotoxic T lymphocyte antigen (CTLA)-4 expression, resistance could be overcome by combination with an anti-CTLA-4 monoclonal antibody (mAb). Patients who responded to combination therapy with anti-PD-1 and anti-CTLA-4 mAbs sequentially after primary resistance to PD-1 blockade monotherapy showed high Treg cell infiltration. We propose that the high antigenicity of Treg cells confers resistance to PD-1 blockade therapy via high PD-1 expression in Treg cells, which can be overcome by combination therapy with an anti-CTLA-4 mAb.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 5","pages":"1214-1226"},"PeriodicalIF":4.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cytoplasmic Vacuolization: A Fascinating Morphological Alteration From Cellular Stress to Cell Death 细胞质空泡化：从细胞应激到细胞死亡的一个令人着迷的形态学改变。

IF 4.5 2区医学

Cancer Science Pub Date : 2025-02-27 DOI: 10.1111/cas.70013

Xiaoxu Wen, Hongru Ma

引用次数: 0

EPHB2 Promotes the Progression of Oral Squamous Cell Carcinoma Cells Through the Activation of VPS4A-Mediated Autophagy EPHB2通过激活vps4a介导的自噬促进口腔鳞状细胞癌细胞的进展。

IF 4.5 2区医学

Cancer Science Pub Date : 2025-02-27 DOI: 10.1111/cas.70033

Yongchun Peng, Jianbo Zhang, Haoxuan Guo, Zhijing He, Yi Jiang, Sheng Zhang, Tengfei Fan

{"title":"EPHB2 Promotes the Progression of Oral Squamous Cell Carcinoma Cells Through the Activation of VPS4A-Mediated Autophagy","authors":"Yongchun Peng, Jianbo Zhang, Haoxuan Guo, Zhijing He, Yi Jiang, Sheng Zhang, Tengfei Fan","doi":"10.1111/cas.70033","DOIUrl":"10.1111/cas.70033","url":null,"abstract":"Oral squamous cell carcinoma (OSCC) is a prevalent type of head and neck neoplasm distinguished by a high risk of metastasis and a poor prognosis. Nevertheless, the fundamental mechanisms of OSCC cell proliferation and metastasis remain poorly understood. Autophagy, as the principal intracellular degradation system, has been implicated in OSCC progression; however, its underlying mechanism remains unclear. In this study, transcriptomic sequencing analysis was performed using both The Cancer Genome Atlas (TCGA) database and samples from OSCC patients and revealed significant upregulation of EPHB2 expression, which is positively correlated with OSCC metastasis and a poor prognosis. In subsequent studies, we observed that the knockdown of EPHB2 resulted in the blockade of autophagic flux due to impaired lysosomal function, leading to inhibited proliferation, migration, and invasion in OSCC cells. Furthermore, the knockdown of EPHB2 significantly suppressed the expression of VPS4A, a key mediator that facilitates autolysosomal degradation. The overexpression of VPS4A restored lysosomal function and autophagic flux, thereby attenuating the inhibitory effects of EPHB2 knockdown on OSCC cell progression. The findings of this study demonstrate that the molecular mechanism underlying EPHB2 regulation of autophagic flux to promote OSCC progression is by regulating VPS4A activity and that EPHB2 may be a diagnostic biomarker and therapeutic target for OSCC prevention and treatment.","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 5","pages":"1308-1323"},"PeriodicalIF":4.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0