Cancer Science最新文献

{"title":"BCR::ABL1-induced mitochondrial morphological alterations as a potential clinical biomarker in chronic myeloid leukemia","authors":"Kohjin Suzuki,&nbsp;Naoki Watanabe,&nbsp;Satoru Torii,&nbsp;Satoko Arakawa,&nbsp;Kiyosumi Ochi,&nbsp;Shun Tsuchiya,&nbsp;Kazuhiro Yamada,&nbsp;Yoko Kawamura,&nbsp;Sadao Ota,&nbsp;Norio Komatsu,&nbsp;Shigeomi Shimizu,&nbsp;Miki Ando,&nbsp;Tomoiku Takaku","doi":"10.1111/cas.16424","DOIUrl":"10.1111/cas.16424","url":null,"abstract":"<p>The <i>BCR::ABL1</i> oncogene plays a crucial role in the development of chronic myeloid leukemia (CML). Previous studies have investigated the involvement of mitochondrial dynamics in various cancers, revealing potential therapeutic strategies. However, the impact of <i>BCR::ABL1</i> on mitochondrial dynamics remains unclear. In this study, we demonstrated that <i>BCR::ABL1</i> is sufficient to induce excessive mitochondrial fragmentation by activating dynamin-related protein (DRP)1 through the mitogen-activated protein kinase (MAPK) pathway. Leukocytes obtained from patients with CML and the <i>BCR::ABL1-</i>positive cell lines exhibited increased mitochondrial fragmentation compared to leukocytes obtained from healthy donors and <i>BCR::ABL1</i>-negative cells. Furthermore, the analysis of <i>BCR::ABL1</i>-transduced cells showed increased phosphorylation of DRP1 at serine 616 and extracellular signal-regulated kinase (ERK) 1/2. Moreover, the inhibition of DRP1 and upstream mitogen-activated extracellular signal-regulated kinase (MEK) 1/2 suppressed mitochondrial fragmentation. Strikingly, DRP1 inhibition effectively reduced the viability of <i>BCR::ABL1</i>-positive cells and induced necrotic cell death. Additionally, a label-free artificial intelligence-driven flow cytometry successfully identified not only the <i>BCR::ABL1</i>-transduced cells but also peripheral leukocytes from CML patients by assessing mitochondrial morphological alterations. These findings suggested the crucial role of <i>BCR::ABL1</i>-induced mitochondrial fragmentation in driving <i>BCR::ABL1</i>-positive cell proliferation, and the potential use of mitochondrial morphological alterations as a clinical biomarker for the label-free detection of CML cells.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 3","pages":"673-689"},"PeriodicalIF":4.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.16424","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802841","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}

{"title":"Cancer-associated fibroblast-derived MMP11 promotes tumor progression in pancreatic cancer","authors":"Zhuoyin Wang,&nbsp;Xu Guo,&nbsp;Xinming Li,&nbsp;Jing Wang,&nbsp;Nengwei Zhang,&nbsp;Buhe Amin,&nbsp;Guangzhong Xu,&nbsp;Bin Zhu","doi":"10.1111/cas.16418","DOIUrl":"10.1111/cas.16418","url":null,"abstract":"<p>Matrix metalloproteinase 11 (MMP11), a zinc-dependent endopeptidase involved in extracellular matrix degradation and remodeling, has been identified as a tumor promoter in multiple cancer types. However, its expression pattern and role in pancreatic ductal adenocarcinoma (PDAC) remain unclear. In this study, elevated MMP11 expression was identified in PDAC tissues and was associated with diminished survival. Integrated single-cell RNA sequencing and co-immunofluorescence staining revealed that MMP11 was predominantly expressed in cancer-associated fibroblasts (CAFs). Mechanistically, cancer cell-derived TGF-β1 mediated CAF activation via the pSmad2/3 pathway and accompanied by MMP11 production. Additionally, MMP11 knockdown in CAFs impaired the proliferative and invasive abilities of AsPC-1 and BxPC-3 cells in vitro; which could be rescued by adding recombinant MMP11. Similarly, co-injection of AsPC-1 cells with MMP11-knockdown CAFs into nude mice significantly suppressed tumor growth and liver metastasis compared with tumors bearing unmodified CAFs. Furthermore, we confirmed that CAF-derived MMP11 may drive the epithelial–mesenchymal transition process of PDAC cells to promote tumor invasion via the PI3K/AKT pathway rather than extracellular matrix remodeling. Collectively, we uncovered a crosstalk between cancer cells and CAFs mediated by TGF-β1 and MMP11 that drives the progression of PDAC.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 3","pages":"643-655"},"PeriodicalIF":4.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.16418","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786881","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}

{"title":"The protective role of anti-parkinsonian drugs in pancreatic cancer risk: A comprehensive case–control study in Taiwan","authors":"Hsuan-Chia Yang,&nbsp;Wen-Chi Chou,&nbsp;Phung-Anh Nguyen,&nbsp;Nhi Thi Hong Nguyen,&nbsp;Nguyen Thi Phuong,&nbsp;Ching-Huan Wang,&nbsp;Jason C. Hsu,&nbsp;Ming-Chin Lin,&nbsp;Chih-Wei Huang","doi":"10.1111/cas.16422","DOIUrl":"10.1111/cas.16422","url":null,"abstract":"<p>Pancreatic cancer is among the deadliest cancers, with a grim prognosis despite advances in treatment. We conducted a population-based case–control study from Taiwan, linking Health and Welfare Data Science Center data to the Taiwan Cancer Registry, which offers a promising strategy for its treatment through drug repurposing. The study aims to identify the association of anti-parkinsonian drugs with pancreatic cancer risk across different age groups. The analysis encompassed 18,921 pancreatic cancer cases and 75,684 matched controls, employing conditional logistic regression to assess the impact of anti-parkinsonian drugs on the risk of pancreatic cancer. Key findings revealed a statistically significant association of the administration with specific anti-parkinsonian medications, including anticholinergic agents, tertiary amines, dopa derivatives, and dopamine receptor agonists, with a reduction in pancreatic cancer risk. These associations were represented as adjusted odds ratios (aORs), ranging from 0.620 (95% CI 0.470–0.810) to 0.764 (95% CI 0.655–0.891). Further, age-stratified analysis revealed variations in efficacy across different age groups. Anticholinergic agents and tertiary amines exhibited greater effectiveness in the 40–64-year age group (aOR, 0.653; 95% CI, 0.489–0.872), whereas dopa derivatives and dopamine receptor agonists were particularly efficacious in the cohort aged ≥65 years (aOR, 0.728; 95% CI, 0.624–0.850 and aOR, 0.665; 95% CI, 0.494–0.894, respectively). Notably, specific drugs such as trihexyphenidyl, levodopa/dopa decarboxylase inhibitor (DDCI), and pramipexole demonstrated a significant decrease in cancer risk, especially in the elderly population. These preliminary findings can contribute to the possible therapeutic role of anti-parkinsonian drugs in the treatment of pancreatic cancer.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 3","pages":"783-791"},"PeriodicalIF":4.5,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.16422","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142773846","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}

{"title":"Comparative analysis of gut microbiota in hormone-sensitive and castration-resistant prostate cancer in Japanese men","authors":"Saizo Fujimoto,&nbsp;Koji Hatano,&nbsp;Eri Banno,&nbsp;Daisuke Motooka,&nbsp;Marco Antonio De Velasco,&nbsp;Yurie Kura,&nbsp;Shingo Toyoda,&nbsp;Mamoru Hashimoto,&nbsp;Shogo Adomi,&nbsp;Takafumi Minami,&nbsp;Kazuhiro Yoshimura,&nbsp;Toshiki Oka,&nbsp;Junya Hata,&nbsp;Makoto Matsushita,&nbsp;Tetsuya Takao,&nbsp;Shingo Takada,&nbsp;Akira Tsujimura,&nbsp;Yasuyuki Kojima,&nbsp;Wataru Obara,&nbsp;Shota Nakamura,&nbsp;Hirotsugu Uemura,&nbsp;Norio Nonomura,&nbsp;Kazutoshi Fujita","doi":"10.1111/cas.16408","DOIUrl":"10.1111/cas.16408","url":null,"abstract":"<p>Gut microbiota plays a crucial role in the development and progression of prostate cancer, with previous studies indicating that certain bacterial taxa are more abundant in castration-resistant prostate cancer (CRPC) compared to hormone-sensitive prostate cancer (HSPC). Notably, the composition of gut microbiota can vary significantly by geographic region, and Japanese individuals have a distinct microbial profile. However, research exploring these differences within Japanese populations remains limited. This study investigated the gut microbiota differences between Japanese men with HSPC and CRPC and further validated these findings using a transgenic mouse model. Rectal swab samples were collected from 140 Japanese men diagnosed with HSPC (<i>n</i> = 84) or CRPC (<i>n</i> = 56) between September 2020 and July 2022. Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Additionally, <i>Pten</i>-KO mice, which model the progression from HSPC to CRPC, underwent similar microbiota analysis. Results revealed significant differences in gut microbiota composition between HSPC and CRPC patients. Specifically, the CRPC group showed a higher abundance of Firmicutes, including <i>Gemella</i> and <i>Lactobacillus</i>, compared to the HSPC group. These differences were mirrored in the mouse model, where CRPC mice also showed an increase in these bacteria. This study identifies distinct microbial differences between HSPC and CRPC in Japanese men, suggesting that <i>Gemella</i> and <i>Lactobacillus</i> may be associated with the progression to castration resistance in prostate cancer. These findings suggest that gut microbiota differences may be associated with prostate cancer progression. Further research is needed to explore the potential of targeting the microbiota as a therapeutic strategy.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 2","pages":"462-469"},"PeriodicalIF":4.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142773806","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}

{"title":"Smoking-independent DNA methylation markers for lung cancer risk: External validation in a large population-based cohort study","authors":"Zitong Zhao,&nbsp;Megha Bhardwaj,&nbsp;Ziwen Fan,&nbsp;Xianzhe Li,&nbsp;Petra Schrotz-King,&nbsp;Hermann Brenner","doi":"10.1111/cas.16414","DOIUrl":"10.1111/cas.16414","url":null,"abstract":"<p>Smoking-associated epigenetic changes have been linked to lung cancer (LC) risk; however, the role of epigenetic alterations independent of smoking is yet to be fully understood. This study aimed to validate 16 previously reported CpG sites that are independent of smoking yet associated with LC risk within a population-based prospective cohort. Using the Infinium Methylation EPIC BeadChip kit or the Infinium HumanMethylation450K BeadChip Assay, DNA methylation (DNAm) in whole blood was assessed in four subsets (<i>n</i> = 736, 1027, 997, and 312) of a population-based cohort from Germany. The DNAm levels of the 16 smoking-independent CpG sites were analyzed. Hazard ratios (HRs) and their 95% confidence intervals (95% CIs) were calculated to assess associations of DNAm at the 16 CpG sites with LC risk, adjusting for multiple covariates, including smoking habits and a smoking-associated DNAm score. Over 17 years of follow-up, a total of 199 LCs were observed. Among the 16 CpGs, cg02211449 showed a negative association with LC risk (HR [95% CI] per SD increase, = 0.70 [0.63–0.78]), while cg11385536 (1.04 [1.01–1.07]), cg09736286 (1.64 [1.10–2.44]), cg19907023 (1.64 [1.01–2.66]), and cg22032485 (1.52 [1.04–2.21]) displayed positive associations with LC risk. Five of the 16 suggested smoking-independent CpGs could be externally validated as predictors of LC risk. Further research should address their potential contribution to enhanced LC risk stratification.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 3","pages":"775-782"},"PeriodicalIF":4.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.16414","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142773825","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}

{"title":"Spatial immune heterogeneity in a mouse tumor model after immunotherapy","authors":"Michal Smahel,&nbsp;Shweta Dilip Johari,&nbsp;Jana Smahelova,&nbsp;Lucie Pfeiferova,&nbsp;Jaroslav Nunvar","doi":"10.1111/cas.16421","DOIUrl":"10.1111/cas.16421","url":null,"abstract":"<p>Cancer immunotherapy is increasingly used in clinical practice, but its success rate is reduced by tumor escape from the immune system. This may be due to the genetic instability of tumor cells, which allows them to adapt to the immune response and leads to intratumoral immune heterogeneity. The study investigated spatial immune heterogeneity in the tumor microenvironment and its possible drivers in a mouse model of tumors induced by human papillomaviruses (HPV) following immunotherapy. Gene expression was determined by RNA sequencing and mutations by whole exome sequencing. A comparison of different tumor areas revealed heterogeneity in immune cell infiltration, gene expression, and mutation composition. While the mean numbers of mutations with every impact on gene expression or protein function were comparable in treated and control tumors, mutations with high or moderate impact were increased after immunotherapy. The genes mutated in treated tumors were significantly enriched in genes associated with ECM metabolism, degradation, and interactions, HPV infection and carcinogenesis, and immune processes such as antigen processing and presentation, Toll-like receptor signaling, and cytokine production. Gene expression analysis of DNA damage and repair factors revealed that immunotherapy upregulated <i>Apobec1</i> and <i>Apobec3</i> genes and downregulated genes related to homologous recombination and translesion synthesis. In conclusion, this study describes the intratumoral immune heterogeneity, that could lead to tumor immune escape, and suggests the potential mechanisms involved.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 3","pages":"622-632"},"PeriodicalIF":4.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.16421","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142773826","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}

{"title":"Reviewers The publication of invaluable papers in Cancer Science depends on the prompt, careful review of submitted manuscripts. We would like to thank the following experts for reviewing manuscripts submitted between October 1, 2023 to September 30, 2024","authors":"","doi":"10.1111/cas.16399","DOIUrl":"https://doi.org/10.1111/cas.16399","url":null,"abstract":"&lt;p&gt;Reviewer names&lt;/p&gt;&lt;p&gt;Yuichi Abe&lt;/p&gt;&lt;p&gt;Naim Abu-Freha&lt;/p&gt;&lt;p&gt;Jun Adachi&lt;/p&gt;&lt;p&gt;Shungo Adachi&lt;/p&gt;&lt;p&gt;Ahmad Adawy&lt;/p&gt;&lt;p&gt;Jiyoung Ahn&lt;/p&gt;&lt;p&gt;Kiwamu Akagi&lt;/p&gt;&lt;p&gt;Yu Akagi&lt;/p&gt;&lt;p&gt;Shusuke Akamatsu&lt;/p&gt;&lt;p&gt;Shinya Akatsuka&lt;/p&gt;&lt;p&gt;Yoshiki Akatsuka&lt;/p&gt;&lt;p&gt;Yoshimitu Akiyama&lt;/p&gt;&lt;p&gt;Kazunari Akiyoshi&lt;/p&gt;&lt;p&gt;Kiyohiro Ando&lt;/p&gt;&lt;p&gt;Masashi Ando&lt;/p&gt;&lt;p&gt;Mizuo Ando&lt;/p&gt;&lt;p&gt;Toshinori Ando&lt;/p&gt;&lt;p&gt;Kenjiro Aogi&lt;/p&gt;&lt;p&gt;Hiroyuki Arai&lt;/p&gt;&lt;p&gt;Seiji Arai&lt;/p&gt;&lt;p&gt;Tomio Arai&lt;/p&gt;&lt;p&gt;Yoshiki Arakawa&lt;/p&gt;&lt;p&gt;Hidetaka Arimura&lt;/p&gt;&lt;p&gt;Tomohiro Arita&lt;/p&gt;&lt;p&gt;Ken Asada&lt;/p&gt;&lt;p&gt;Shuhei Asada&lt;/p&gt;&lt;p&gt;Hajime Asahina&lt;/p&gt;&lt;p&gt;Kazuo Asanoma&lt;/p&gt;&lt;p&gt;Kunihiro Asanuma&lt;/p&gt;&lt;p&gt;Tetsuhiko Asao&lt;/p&gt;&lt;p&gt;Yoshinari Asaoka&lt;/p&gt;&lt;p&gt;Eishi Ashihara&lt;/p&gt;&lt;p&gt;William Atiomo&lt;/p&gt;&lt;p&gt;Kotaro Azuma&lt;/p&gt;&lt;p&gt;Eishi Baba&lt;/p&gt;&lt;p&gt;Hideo Baba&lt;/p&gt;&lt;p&gt;Tsukasa Baba&lt;/p&gt;&lt;p&gt;Yoshifumi Baba&lt;/p&gt;&lt;p&gt;Mohamadreza K Bakht&lt;/p&gt;&lt;p&gt;Oluwaseun Adebayo Bamodu&lt;/p&gt;&lt;p&gt;Lyudmila Bel'Skaya&lt;/p&gt;&lt;p&gt;Prateek Bhatia&lt;/p&gt;&lt;p&gt;Sergei Boichuk&lt;/p&gt;&lt;p&gt;Horacio Cabral&lt;/p&gt;&lt;p&gt;Shang Cai&lt;/p&gt;&lt;p&gt;Kaixiang Cao&lt;/p&gt;&lt;p&gt;Carmine Carbone&lt;/p&gt;&lt;p&gt;Joaquim Carreras&lt;/p&gt;&lt;p&gt;Michael Chan&lt;/p&gt;&lt;p&gt;Yongsheng Jason Chan&lt;/p&gt;&lt;p&gt;Jianfeng Chang&lt;/p&gt;&lt;p&gt;Hadrien Charvat&lt;/p&gt;&lt;p&gt;Liang Chen&lt;/p&gt;&lt;p&gt;Yang Chen&lt;/p&gt;&lt;p&gt;Zhiyu Chen&lt;/p&gt;&lt;p&gt;Pu Cheng&lt;/p&gt;&lt;p&gt;Ying-Cheng Chiang&lt;/p&gt;&lt;p&gt;Hideki Chiba&lt;/p&gt;&lt;p&gt;Natsuko Chiba&lt;/p&gt;&lt;p&gt;Shigeru Chiba&lt;/p&gt;&lt;p&gt;Kazuaki Chikamatsu&lt;/p&gt;&lt;p&gt;Tatsuyuki Chiyoda&lt;/p&gt;&lt;p&gt;Weimin Ci&lt;/p&gt;&lt;p&gt;Samuel Cohen&lt;/p&gt;&lt;p&gt;Laura Cortesi&lt;/p&gt;&lt;p&gt;Karen Crasta&lt;/p&gt;&lt;p&gt;Haruko Daga&lt;/p&gt;&lt;p&gt;Takiko Daikoku&lt;/p&gt;&lt;p&gt;Shingo Dan&lt;/p&gt;&lt;p&gt;Santanu Dasgupta&lt;/p&gt;&lt;p&gt;Thomas Daubon&lt;/p&gt;&lt;p&gt;Ayako Demachi-Okamura&lt;/p&gt;&lt;p&gt;Yosuke Demizu&lt;/p&gt;&lt;p&gt;Jie Dong&lt;/p&gt;&lt;p&gt;Dan Duda&lt;/p&gt;&lt;p&gt;Hidetoshi Eguchi&lt;/p&gt;&lt;p&gt;Takanori Eguchi&lt;/p&gt;&lt;p&gt;Shogo Ehata&lt;/p&gt;&lt;p&gt;Elamin H Elbasha&lt;/p&gt;&lt;p&gt;Yutaka Endo&lt;/p&gt;&lt;p&gt;Daisuke Ennishi&lt;/p&gt;&lt;p&gt;Hideki Enokida&lt;/p&gt;&lt;p&gt;N. E. Ezinne&lt;/p&gt;&lt;p&gt;Dong Fang&lt;/p&gt;&lt;p&gt;Weijia Fang&lt;/p&gt;&lt;p&gt;Fan Feng&lt;/p&gt;&lt;p&gt;Hirofumi Fujii&lt;/p&gt;&lt;p&gt;Satoshi Fujii&lt;/p&gt;&lt;p&gt;Shin-Ichiro Fujii&lt;/p&gt;&lt;p&gt;Atsushi Fujimura&lt;/p&gt;&lt;p&gt;Takao Fujisawa&lt;/p&gt;&lt;p&gt;Mitsuhiro Fujishiro&lt;/p&gt;&lt;p&gt;Teruaki Fujishita&lt;/p&gt;&lt;p&gt;Kazutoshi Fujita&lt;/p&gt;&lt;p&gt;Hiroshi Fujiwara&lt;/p&gt;&lt;p&gt;Naoto Fujiwara&lt;/p&gt;&lt;p&gt;Yukio Fujiwara&lt;/p&gt;&lt;p&gt;Tomoya Fukawa&lt;/p&gt;&lt;p&gt;Akihisa Fukuda&lt;/p&gt;&lt;p&gt;Shinji Fukuda&lt;/p&gt;&lt;p&gt;Shigetomo Fukuhara&lt;/p&gt;&lt;p&gt;Keisuke Fukui&lt;/p&gt;&lt;p&gt;Hidenori Fukuoka&lt;/p&gt;&lt;p&gt;Noriyoshi Fukushima&lt;/p&gt;&lt;p&gt;Itoh Fumiko&lt;/p&gt;&lt;p&gt;Ryo Funayama&lt;/p&gt;&lt;p&gt;Tatsuhiko Furukawa&lt;/p&gt;&lt;p&gt;Tatsuhiko Furukawa&lt;/p&gt;&lt;p&gt;Toru Furukawa&lt;/p&gt;&lt;p&gt;Yusuke Furukawa&lt;/p&gt;&lt;p&gt;Mikio Furuse&lt;/p&gt;&lt;p&gt;Mitsuru Futakuchi&lt;/p&gt;&lt;p&gt;Ping Gao&lt;/p&gt;&lt;p&gt;Yuzhen Gao&lt;/p&gt;&lt;p&gt;Min Gi&lt;/p&gt;&lt;p&gt;Hidemasa Goto&lt;/p&gt;&lt;p&gt;Osamu Gotoh&lt;/p&gt;&lt;p&gt;Adam L. Green&lt;/p&gt;&lt;p&gt;Hiroshi Haeno&lt;/p&gt;&lt;p&gt;Shin Hamada&lt;/p&gt;&lt;p&gt;Tsuyoshi Hamada&lt;/p&gt;&lt;p&gt;Yoichiro Hamamoto&lt;/p&gt;&lt;p&gt;Junzo Hamanishi&lt;/p&gt;&lt;p&gt;Yasushi Hamaya&lt;/p&gt;&lt;p&gt;Ichiro Hanamura&lt;/p&gt;&lt;p&gt;Megumi Hara&lt;/p&gt;&lt;p&gt;Tomoaki Hara&lt;/p&gt;&lt;p&gt;Hiroshi Harada&lt;/p&gt;&lt;p&gt;Kenji Harada&lt;/p&gt;&lt;p&gt;Naoaki Harada&lt;/p&gt;&lt;p&gt;Yoichiro Harada&lt;/p&gt;&lt;p&gt;Koji Haratani&lt;/p&gt;&lt;p&gt;Koichiro Haruki&lt;/p&gt;&lt;p&gt;Ari Hashimoto&lt;/p&gt;&lt;p&gt;Naoya Hashimoto&lt;/p&gt;&lt;p&gt;Shinichi Hashimoto&lt;/p&gt;&lt;p&gt;Tadayoshi Hashimoto&lt;/p&gt;&lt;p&gt;Nobuhiro Hata&lt;/p&gt;&lt;p&gt;Ryusuke Hatae&lt;/p&gt;&lt;p&gt;Shigetsugu Hatakeyama&lt;/p&gt;&lt;p&gt;Etsuro Hatano&lt;/p&gt;&lt;p&gt;Naoko Hattori&lt;/p&gt;&lt;p&gt;Fumihiko Hayakawa&lt;/p&gt;&lt;p&gt;Yoku Hayakawa&lt;/p&gt;&lt;p&gt;Hidetoshi Ha","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 12","pages":"4074-4079"},"PeriodicalIF":4.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.16399","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764007","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}

{"title":"Exploring the tumor microenvironment of colorectal cancer patients post renal transplantation by single-cell analysis","authors":"Jinghui Zhang,&nbsp;Yusuke Mizuuchi,&nbsp;Kenoki Ohuchida,&nbsp;Kyoko Hisano,&nbsp;Yuki Shimada,&nbsp;Naoki Katayama,&nbsp;Chikanori Tsutsumi,&nbsp;Bryan C. Tan,&nbsp;Kinuko Nagayoshi,&nbsp;Koji Tamura,&nbsp;Takaaki Fujimoto,&nbsp;Naoki Ikenaga,&nbsp;Kohei Nakata,&nbsp;Yoshinao Oda,&nbsp;Masafumi Nakamura","doi":"10.1111/cas.16409","DOIUrl":"10.1111/cas.16409","url":null,"abstract":"<p>Patients with colorectal cancer (CRC) following renal transplantation require long-term immunosuppressants to prevent graft rejection. However, the impact of these immunosuppressants on the tumor immune microenvironment and the roles of immune cells within it remain poorly understood. We conducted comprehensive single-cell RNA sequencing on tumor and normal tissues from four CRC patients post renal transplantation and compared these with published data from 23 non-transplant CRC patients. We set four groups for detailed comparative analysis based on the renal transplantation status and tissue origin: non-renal transplantation normal (nRT_Normal), non-renal transplantation tumor (nRT_Tumor), renal transplantation normal (RT_Normal), renal transplantation tumor (RT_Tumor). Our analysis revealed significant tumor immune microenvironment landscape alterations in the transplantation group. CD8⁺effector T cells of RT_Tumor showed significantly diminished cytotoxicity and tumor neoantigen recognition (<i>p</i> &lt; 0.0001), while CD4⁺FOXP3 regulatory T cells of RT_Tumor displayed a higher inhibitory score (<i>p</i> &lt; 0.05), indicating preserved immunomodulatory potential compared with non-transplant CRC. Notably, significantly increased CTLA4 expression in T cells of RT_Tumor was found and testified (<i>p</i> &lt; 0.05). Our findings provide novel mechanistic insights for understanding the immune landscape in renal transplant recipients with CRC and pave the way for potential immunotherapeutic strategies that may improve survival and quality of life for this patient population.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 2","pages":"500-512"},"PeriodicalIF":4.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142773809","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}

{"title":"LncRNA MIR600HG inhibits laryngeal cancer development by mediating the miR-424-5p/BTG2 axis","authors":"Xiaowen Zhu,&nbsp;Min Zhong,&nbsp;Qingdong Wang,&nbsp;MeiJia Zhang","doi":"10.1111/cas.16404","DOIUrl":"10.1111/cas.16404","url":null,"abstract":"<p>Laryngeal carcinoma is the predominant kind of tumor seen under the category of head and neck malignancies. LncRNA MIR600HG affects tumor morphology in numerous cancer types. However, the function of MIR600HG in laryngeal cancer remains unclear. Protein and gene expressions were analyzed by using western blot and quantitative real time polymerase chain reaction. Cells proliferation and migration were evaluated by EdU and transwell assays. Flow cytometry was performed to detect cells apoptosis. The interaction between MIR600HG or B-cell translocation gene 2 (BTG2) and miR-424-5p was analyzed by dual luciferase reporter assay and RNA immunoprecipitation. The expression of MIR600HG in laryngeal cancer tissues was lower than that in normal tissues, and low expression of MIR600HG was associated with poor prognosis in laryngeal cancer. Furthermore, overexpression of MIR600HG resulted in a reduction in cellular proliferation and the promotion of apoptosis in both HEp-2 and Tu-212. Mechanically, miR-424-5p was a direct target of MIR600HG, and overexpression of MIR600HG reduced miR-424-5p expression. Furthermore, BTG2 was a target gene of miR-424-5p and miR-424-5p upregulation suppressed the expression of BTG2. In addition, overexpression of BTG2 inhibited laryngeal cancer progression, whereas MIR600HG knockdown or miR-424-5p overexpression reversed the role of BTG2. This work suggested that MIR600HG represses laryngeal tumor development by regulating the miR-424-5p/BTG2 axis, which provides new molecules for early diagnosis of laryngeal cancer in the future.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 2","pages":"544-558"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142773810","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}

{"title":"GPNMB is a novel binding partner of FGFR1 that affects tumorigenic potential through AKT phosphorylation in TNBC","authors":"Manar A. Elhinnawi,&nbsp;Yukari Okita,&nbsp;Katsunobu Shigematsu,&nbsp;Mohammed Abdelaziz,&nbsp;Rie Shiratani,&nbsp;Kunio Kawanishi,&nbsp;Kowit Hengphasatporn,&nbsp;Thuy Linh Dang Cao,&nbsp;Yasuteru Shigeta,&nbsp;Mitsuyasu Kato","doi":"10.1111/cas.16419","DOIUrl":"10.1111/cas.16419","url":null,"abstract":"<p>Breast cancer is a heterogeneous disease and is one of the most prevalent cancers in women. Triple-negative breast cancer (TNBC) is a relatively aggressive subtype of breast cancer, which is difficult to treat. Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a type I transmembrane protein that is overexpressed in various types of cancers, including breast cancer, especially TNBC. In this study, bioinformatic analyses revealed enhanced fibroblast growth factor receptor 1 (FGFR1) signaling in patients with invasive breast cancer, and the <i>GPNMB</i>^high/<i>FGFR1</i>^high group exhibited a lower probability of relapse-free survival (RFS) than the <i>GPNMB</i>^low/<i>FGFR1</i>^low group. Additionally, we observed that GPNMB and FGFR1 were essential for sphere formation, cellular migration, and epithelial-mesenchymal transition (EMT)-like changes in TNBC cells. To explore the mutual interaction between these two molecules, we conducted in silico protein–protein docking studies and molecular dynamics simulations. The results revealed that GPNMB isoform b exhibits high binding affinity for FGFR1 isoform c (FGFR1c), which correlates with cancer aggressiveness. We also confirmed the interaction between GPNMB and FGFR1 in TNBC cells. Furthermore, our study demonstrated that GPNMB is essential for AKT phosphorylation at T308 following FGF2 stimulation, resulting in high affinity for FGFR1c. Inhibition of AKT phosphorylation substantially reduces the tumorigenic potential of TNBC cells.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 2","pages":"432-443"},"PeriodicalIF":4.5,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752195","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}