Cancer letters最新文献_第2页

Targeting the VIP-VPAC Pathway in Melanoma Models Inhibits Tumor Growth and Liver Metastasis 靶向黑色素瘤模型VIP-VPAC通路抑制肿瘤生长和肝转移

IF 9.1 1区医学

Cancer letters Pub Date : 2025-06-05 DOI: 10.1016/j.canlet.2025.217855

Wenxi Wang , Hua Yang , Tenzin Passang , Yiwen Li , Hanwen Zhang , Shayna E. Jankowski , Fanyuan Zeng , Shuhua Wang , Po-Chih Hsu , Jian-Ming Li , Zihan Chen , Gregory B. Lesinski , Pia R. Mendoza , Ying Li , Cynthia R. Giver , Hans E. Grossniklaus , Edmund K. Waller

{"title":"Targeting the VIP-VPAC Pathway in Melanoma Models Inhibits Tumor Growth and Liver Metastasis","authors":"Wenxi Wang , Hua Yang , Tenzin Passang , Yiwen Li , Hanwen Zhang , Shayna E. Jankowski , Fanyuan Zeng , Shuhua Wang , Po-Chih Hsu , Jian-Ming Li , Zihan Chen , Gregory B. Lesinski , Pia R. Mendoza , Ying Li , Cynthia R. Giver , Hans E. Grossniklaus , Edmund K. Waller","doi":"10.1016/j.canlet.2025.217855","DOIUrl":"10.1016/j.canlet.2025.217855","url":null,"abstract":"<div><div>Uveal melanoma (UVM) is resistant to immune checkpoint therapy and chemotherapy, resulting in high mortality rates, primarily due to liver metastases. While vasoactive intestinal peptide (VIP) signaling has been identified as an immune checkpoint and therapeutic target in pancreatic cancer, its role in melanoma remains unexplored. This study investigated the impact of a novel VIP receptor antagonist, ANT308, on melanoma cell behavior and tumor growth. Using both murine and human UVM/cutaneous melanoma cell lines, we examined the inhibition of VIP receptor signaling and its effects on cell migration and proliferation <em>in vitro</em>. Mechanistically, ANT308 downregulated melanoma cell adhesion molecule (MCAM) and N-cadherin expression at both the RNA and protein levels, as demonstrated by RNA sequencing and Western blot analyses. Knockdown of the VIP receptor VPAC2 in mouse and human melanoma cells produced similar effects on cell migration, proliferation, and MCAM protein expression, further implicating VIP-VPAC2 signaling in tumor progression. <em>In vivo</em> studies revealed that ANT308 treatment decreased MCAM expression in intraocular primary tumors, reduced the number and size of liver metastases following intraocular or subcutaneous melanoma injection, and showed a trend toward reduced tumor volume at the primary tumor site. In conclusion, our findings indicate that VIP receptor signaling promotes liver metastasis in melanoma, and targeting this pathway with VIP receptor antagonists may represent a novel therapeutic strategy for treating metastatic UVM.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"628 ","pages":"Article 217855"},"PeriodicalIF":9.1,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advancing Neoadjuvant Therapy with Inetetamab for HER2-Positive Breast Cancer. 英替他单抗治疗her2阳性乳腺癌的新辅助治疗进展

IF 9.1 1区医学

Cancer letters Pub Date : 2025-06-05 DOI: 10.1016/j.canlet.2025.217852

Wenbin Zhou, Qiang Ding

{"title":"Advancing Neoadjuvant Therapy with Inetetamab for HER2-Positive Breast Cancer.","authors":"Wenbin Zhou, Qiang Ding","doi":"10.1016/j.canlet.2025.217852","DOIUrl":"https://doi.org/10.1016/j.canlet.2025.217852","url":null,"abstract":"<p><p>HER2-positive breast cancer accounts for approximately 15% to 20% of all breast cancer cases and is typically characterized by aggressive tumor biology, an elevated risk of recurrence, and poor long-term survival [1]. Although HER2-targeted therapies such as trastuzumab and pertuzumab result in significantly improved clinical outcomes, the total pathological complete response (tpCR) rate remains suboptimal, particularly among hormone receptor (HR)-positive patients [2]. Neoadjuvant therapy plays a critical role in facilitating tumor downstaging in locally advanced cases and provides a valuable opportunity to evaluate therapeutic efficacy and guide adjuvant treatment. Consequently, the development of novel anti-HER2 agents and combination strategies has become a major focus of ongoing researches. Inetetamab, a humanized monoclonal antibody targeting HER2 with an engineered Fc domain to enhance antibody-dependent cellular cytotoxicity, represents a promising candidate for improving treatment outcomes [3, 4]. In this issue of Cancer Letters, Zuo and colleagues present findings from a single-arm, multicenter phase II clinical trial investigating a neoadjuvant regimen combining inetetamab, pertuzumab, and nab-paclitaxel (TIP regimen) in patients with early-stage or locally advanced HER2-positive breast cancer [5]. Through comprehensive evaluation of both efficacy and safety, the study demonstrates exceptional therapeutic potential of the TIP regimen, with a high tpCR rate observed in estrogen receptor (ER)-negative patients, indicating particular promise for this subgroup of HER2-positive breast cancer.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217852"},"PeriodicalIF":9.1,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CHD4 drives gastric cancer metastasis via MYH9/GSK3β/β-catenin axis and WNT/EMT pathway activation CHD4通过MYH9/GSK3β/β-catenin轴和WNT/EMT通路激活驱动胃癌转移

IF 9.1 1区医学

Cancer letters Pub Date : 2025-06-04 DOI: 10.1016/j.canlet.2025.217813

Yuntao Shi , Zidan Zhao , Shangbo Zhou , Ziwen Zhou , Zhangsen Huang , Zhijun Zhou , Changhua Zhang

{"title":"CHD4 drives gastric cancer metastasis via MYH9/GSK3β/β-catenin axis and WNT/EMT pathway activation","authors":"Yuntao Shi , Zidan Zhao , Shangbo Zhou , Ziwen Zhou , Zhangsen Huang , Zhijun Zhou , Changhua Zhang","doi":"10.1016/j.canlet.2025.217813","DOIUrl":"10.1016/j.canlet.2025.217813","url":null,"abstract":"<div><div>Gastric cancer (GC) metastasis remains a significant cause of cancer-related mortality, yet the molecular mechanisms underlying this process have not been fully elucidated. CHD4, a chromatin remodeling factor, has been associated with oncogenic processes, but its precise role in GC metastasis has not been defined. In this study, we identify CHD4 as a critical regulator of GC metastasis through the MYH9/GSK3β/β-catenin axis and the activation of the WNT pathway and epithelial–mesenchymal transition (EMT). Clinically, CHD4 was significantly overexpressed in GC tissues and strongly correlated with advanced disease stages and poor prognosis. Mechanistically, CHD4 interacted with MYH9 via its ATPase domain and promoted the nuclear-to-cytoplasmic translocation of MYH9, thereby enabling MYH9 to orchestrate inhibitory phosphorylation and ubiquitination-dependent degradation of GSK3β. This, in turn, stabilized β-catenin, leading to its nuclear accumulation and activation of downstream WNT target genes, such as Cyclin D1, along with the induction of EMT. Functionally, suppression of CHD4 expression inhibited GC cell migration, invasion, and metastasis in vivo, while MYH9 restoration reversed these effects. Collectively, these findings establish CHD4 as a key regulator of GC metastasis through the MYH9/GSK3β/β-catenin axis and underscore its potential as a therapeutic target for inhibiting GC progression.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"628 ","pages":"Article 217813"},"PeriodicalIF":9.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144242000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transarterial chemoembolization combined with intra-arterial infusion of sintilimab and bevacizumab for advanced hepatocellular carcinoma: a phase 2 study 经动脉化疗栓塞联合动脉内输注辛替单抗和贝伐单抗治疗晚期肝细胞癌：一项2期研究

IF 9.1 1区医学

Cancer letters Pub Date : 2025-06-03 DOI: 10.1016/j.canlet.2025.217851

Mao-Yuan Mu , Zi-Xiong Chen , Yu-Zhe Cao , Xiao-Bo Fu , Li-Jie Qiu , Han Qi , Fei Gao

{"title":"Transarterial chemoembolization combined with intra-arterial infusion of sintilimab and bevacizumab for advanced hepatocellular carcinoma: a phase 2 study","authors":"Mao-Yuan Mu , Zi-Xiong Chen , Yu-Zhe Cao , Xiao-Bo Fu , Li-Jie Qiu , Han Qi , Fei Gao","doi":"10.1016/j.canlet.2025.217851","DOIUrl":"10.1016/j.canlet.2025.217851","url":null,"abstract":"<div><div>Transarterial chemoembolization (TACE) is an effective locoregional treatment for unresectable hepatocellular carcinoma (HCC). Arterial administration can enhance local drug concentrations while reducing systemic toxicity. The potential synergistic effects of combining locoregional treatments with systemic therapy in advanced HCC warrant further investigation. This phase 2 study (NCT04796025) aimed to evaluate the efficacy and safety of TACE combined with intra-arterial infusion of sintilimab and bevacizumab in patients with advanced HCC. Eligible patients received TACE on demand plus intra-arterial infusion of sintilimab and bevacizumab for four cycles. Maintenance therapy included intravenous administration of sintilimab and bevacizumab until disease progression or unacceptable side effects. The primary outcome was the objective response rate (ORR) based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST). A total of 34 patients (median age, 53 years [IQR 45–59]; 33 men) were enrolled. With a median follow-up of 10.3 months (IQR 5.8–15.6), our results showed a favorable ORR of 70.6 %. The median PFS was calculated as 6.0 months (95 % CI 4.8 - not reached), and the median OS was 12.2 months (95 % CI 9.3 - not reached). Common treatment-related adverse events (any grade) included elevated alanine transaminase (17.6 %), abdominal pain (14.7 %), elevated aspartate aminotransferase (11.8 %), and hypertension (11.8 %). Grade 3 adverse events included hypertension (2.9 %) and gastrointestinal hemorrhage (8.8 %). No serious treatment-related adverse events were observed. TACE combined with sintilimab and bevacizumab has demonstrated a favorable ORR and promising efficacy in advanced HCC, with manageable side effects.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"628 ","pages":"Article 217851"},"PeriodicalIF":9.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pan-cancer analysis reveals multifaceted roles of nonmyelinating Schwann cells in gastrointestinal cancers 泛癌分析揭示了非髓鞘性雪旺细胞在胃肠道癌症中的多方面作用

IF 9.1 1区医学

Cancer letters Pub Date : 2025-06-03 DOI: 10.1016/j.canlet.2025.217850

Hui Li , Luju Jiang , Shan Zhang , Xiaocao Miao , Shu-Heng Jiang

{"title":"Pan-cancer analysis reveals multifaceted roles of nonmyelinating Schwann cells in gastrointestinal cancers","authors":"Hui Li , Luju Jiang , Shan Zhang , Xiaocao Miao , Shu-Heng Jiang","doi":"10.1016/j.canlet.2025.217850","DOIUrl":"10.1016/j.canlet.2025.217850","url":null,"abstract":"<div><div>Cancer neuroscience has emerged as a pivotal interdisciplinary field, offering transformative insights into tumor progression mechanisms. Nonmyelinating Schwann cells (NMSCs), integral yet understudied components of the tumor microenvironment (TME), exhibit complex roles in modulating tumor malignancy. Here, we employed deconvolution algorithms to quantify NMSC enrichment by leveraging bulk RNA-seq data. By integrating multi-omics and single-cell strategies along with comprehensive bioinformatics analyses, we delineated NMSC-mediated regulatory networks and their functional impact on gastrointestinal tumors. NMSC enrichment strongly correlated with core cancer hallmarks, notably “Activating invasion and metastasis” and “Inducing angiogenesis”. Immune profiling revealed NMSCs as multifaceted regulators of the TME: positively associated with myeloid-derived suppressor cells, natural killer cells, and regulatory T cells, but inversely correlated with CD56dim NK cells, monocytes, and neutrophils. Genomic analyses uncovered nuanced associations between NMSC abundance and somatic mutations, copy number variation, and methylation patterns, while microRNA mapping highlighted NMSC-specific networks. Single-cell resolution analysis demonstrated that NMSCs engage epithelial cells and fibroblasts via extracellular matrix-centric signaling axes. Collectively, our findings establish NMSCs as multifaceted TME orchestrators, providing mechanistic rationale for NMSC-targeted diagnostic biomarkers and stromal reprogramming therapies in precision oncology.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"628 ","pages":"Article 217850"},"PeriodicalIF":9.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to "METTL3-mediated HSPA9 m6A modification promotes malignant transformation and inhibits cellular senescence by regulating exosomal mortalin protein in cervical cancer" [Cancer Lett. 587 (2024) 216658]. “mettl3介导的hspa9m6a修饰通过调节外泌体死亡蛋白促进宫颈癌的恶性转化和抑制细胞衰老”[癌症杂志]. 587(2024)216658。

IF 9.1 1区医学

Cancer letters Pub Date : 2025-06-03 DOI: 10.1016/j.canlet.2025.217827

Keyi Ao, Minuo Yin, Xiaoming Lyu, Yue Xiao, Xiaona Chen, Sheng Zhong, Xiuli Wen, Jianli Yuan, Ming Ye, Jiaming Zhang, Xin Li, Yi Hao, Xia Guo

引用次数: 0

Corrigendum to "Efficacy of the first-line immune checkpoint inhibitor plus chemotherapy for gastroesophageal cancer: A meta-analysis of phase III trials including unreported PD-L1 subgroups" [Cancer Lett. 623, (2025) 217718]. 《一线免疫检查点抑制剂联合化疗治疗胃食管癌的疗效：包括未报道的PD-L1亚组的III期试验的荟萃分析》的勘误表[癌症杂志，623,(2025)217718]。

IF 9.1 1区医学

Cancer letters Pub Date : 2025-06-03 DOI: 10.1016/j.canlet.2025.217826

Choong-Kun Lee, Sejung Park, Yaeji Lee, Choa Yun, Moonki Hong, Chung Mo Nam, Hyun Cheol Chung, Sun Young Rha

引用次数: 0

Tumor-associated Schwann cells promote salivary adenoid cystic carcinoma stem-like reprogramming via IGF2/IGF1R induced histone H3 lysine 18 lactylation 肿瘤相关的雪旺细胞通过IGF2/IGF1R诱导的组蛋白H3赖氨酸18乙酰化促进唾液腺样囊性癌干细胞样重编程。

IF 9.1 1区医学

Cancer letters Pub Date : 2025-06-02 DOI: 10.1016/j.canlet.2025.217847

Su Chen , Guangzhao Huang , Zhiyong Guo , Zijian Guo , Chang Cao , Guile Zhao , Grace Paka Lubamba , Yuncong Huang , Jiajin Yang , Haosen Lian , Yufei Hua , Cheng Miao , Jiefei Shen , Ming Xuan , Xiufa Tang , Zhangfan Ding , Chunjie Li

{"title":"Tumor-associated Schwann cells promote salivary adenoid cystic carcinoma stem-like reprogramming via IGF2/IGF1R induced histone H3 lysine 18 lactylation","authors":"Su Chen , Guangzhao Huang , Zhiyong Guo , Zijian Guo , Chang Cao , Guile Zhao , Grace Paka Lubamba , Yuncong Huang , Jiajin Yang , Haosen Lian , Yufei Hua , Cheng Miao , Jiefei Shen , Ming Xuan , Xiufa Tang , Zhangfan Ding , Chunjie Li","doi":"10.1016/j.canlet.2025.217847","DOIUrl":"10.1016/j.canlet.2025.217847","url":null,"abstract":"<div><div>Salivary adenoid cystic carcinoma (SACC) is characterized by an exceptionally dense neural network within its tumor microenvironment. Schwann cells (SCs), an essential component of this neural network, have recently emerged as critical mediators of tumor progression. However, SACC-induced SCs reprogramming, as well as the functional significance and molecular mechanisms of tumor-associated Schwann cells (TA-SCs), remains largely elusive. We employed tissue-clearing-based three-dimensional imaging to evaluate the SACC tumor microenvironment with high spatial resolution. We also characterized SCs heterogeneity using single-cell RNA sequencing data from GEO. We investigated the biological phenotypes transformation and revealed the transcriptome characteristics of TA-SCs in SACC, indicating that TGF-β1 exerts its function through c-Jun activation, which is pivotal for driving TA-SCs reprogramming. Furthermore, we determined that TA-SCs enhance SACC cell proliferation, migration, invasion, cisplatin resistance, and stemness. We further discovered that TA-SCs elevate histone lactylation in SACC via paracrine IGF2 signaling. Inhibition of IGF2/IGF1R signaling curbed histone H3 lysine 18 lactylation (H3K18la) in SACC and attenuated the IGF2-driven stem-like reprogramming effect, while simultaneous blockade of TGF-βR1 and IGF1R activation maximally restricted this reprogramming. These findings underscore the pivotal role of TA-SCs in SACC progression and stem-like reprogramming via IGF2/IGF1R-H3K18la axis, representing promising therapeutic targets for this malignancy.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"628 ","pages":"Article 217847"},"PeriodicalIF":9.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cell differentiation-related signaling pathways in hepatocellular carcinoma metastasis 肝细胞癌转移中细胞分化相关信号通路的研究

IF 9.1 1区医学

Cancer letters Pub Date : 2025-05-31 DOI: 10.1016/j.canlet.2025.217846

Ze Xiang , Jiarui Li , Yunyang Xu , Chenhao Xu , Shusen Zheng , Jian Chen , Xuyong Wei , Xiao Xu

{"title":"Cell differentiation-related signaling pathways in hepatocellular carcinoma metastasis","authors":"Ze Xiang , Jiarui Li , Yunyang Xu , Chenhao Xu , Shusen Zheng , Jian Chen , Xuyong Wei , Xiao Xu","doi":"10.1016/j.canlet.2025.217846","DOIUrl":"10.1016/j.canlet.2025.217846","url":null,"abstract":"<div><div>Primary liver cancer is the third leading cause of cancer-related deaths worldwide, with persistently high incidence and mortality rates. Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, has a complex pathogenesis. Moreover, due to the low rate of early diagnosis and limited treatment options, the prognosis for HCC patients is poor, with a median overall survival of approximately one year for advanced-stage HCC. Cancer metastasis is one of the main reasons for HCC-related deaths. During the metastatic process, tumor cells undergo a series of complex biological changes, including epithelial-mesenchymal transition, extracellular matrix remodeling, angiogenesis, and resistance to anoikis, which are key steps. These changes promote the invasion and migration of tumor cells and are central mechanisms of cancer progression. In the metastatic process of HCC, signaling pathways that regulate cell proliferation, differentiation, and apoptosis, such as Hippo-YAP/TAZ, Wnt/β-catenin, Notch, Hedgehog and JAK/STAT, become dysregulated and play a promoting role in the aggressive growth and distant migration of HCC cells. Treatment strategies targeting these pathways are currently being developed. These new agents, being more targeted, may have better tolerability and fewer adverse effects. This review focuses on the role of these key signaling pathways in the metastatic process of HCC and summarizes the treatment strategies targeting these pathways.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"627 ","pages":"Article 217846"},"PeriodicalIF":9.1,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of 7-dehydrocholesterol in inducing ER stress and apoptosis of head and neck squamous cell carcinoma 7-脱氢胆固醇在头颈部鳞状细胞癌内质网应激及凋亡中的作用。

IF 9.1 1区医学

Cancer letters Pub Date : 2025-05-31 DOI: 10.1016/j.canlet.2025.217842

Bok-Soon Lee , Yea-In Park , Hengtian Liu , Sang Gyu Kim , Hyo Jeong Kim , Ji-Hye Choi , Si Hyun Rho , Joselyn Padilla , Jin Roh , Hyun Goo Woo , Hae Jin Seo , Man Ho Choi , Yu-Jin Jeong , Evan C. Lien , Syed Hassan Mehdi , Dongjoon Lee , Donghoon Yoon , Chul-Ho Kim , Jiyoung Lee

{"title":"The role of 7-dehydrocholesterol in inducing ER stress and apoptosis of head and neck squamous cell carcinoma","authors":"Bok-Soon Lee , Yea-In Park , Hengtian Liu , Sang Gyu Kim , Hyo Jeong Kim , Ji-Hye Choi , Si Hyun Rho , Joselyn Padilla , Jin Roh , Hyun Goo Woo , Hae Jin Seo , Man Ho Choi , Yu-Jin Jeong , Evan C. Lien , Syed Hassan Mehdi , Dongjoon Lee , Donghoon Yoon , Chul-Ho Kim , Jiyoung Lee","doi":"10.1016/j.canlet.2025.217842","DOIUrl":"10.1016/j.canlet.2025.217842","url":null,"abstract":"<div><div>Alterations of metabolic pathways that sustain cancer cell survival often offer promising therapeutic avenues. Here, we show that enhanced <em>de novo</em> cholesterol biosynthesis is crucial for the survival of head and neck squamous cell carcinoma (HNSCC). Transcriptomic analysis of HNSCC tissues identified profound dysregulation in steroid and cholesterol metabolism compared to normal tissues. Inhibition of two key enzymes, DHCR7 and DHCR24, which mediate cholesterol biosynthesis, induced apoptosis in HNSCC cells, even when cholesterol levels were restored. Metabolomic profiling revealed the accumulation of 7-dehydrocholesterol (7-DHC) upon DHCR7 or DHCR24 inhibition, triggering endoplasmic reticulum (ER) stress and promoting further cell death. These findings suggest that HNSCC cells adapt to ER stress by modulating 7-DHC levels through enhancing DHCR7 and DHCR24 levels, highlighting a metabolic vulnerability in HNSCC and demonstrating a direct link between cholesterol metabolism and ER stress in cancer cell viability.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"628 ","pages":"Article 217842"},"PeriodicalIF":9.1,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0