Molecular Cancer Research最新文献_第10页

ETS1, a target gene of the EWSR1::FLI1 fusion oncoprotein, regulates the expression of the focal adhesion protein TENSIN3 EWSR1::FLI1融合肿瘤蛋白的靶基因ETS1调控局灶粘附蛋白TENSIN3的表达

IF 5.2 2区医学

Molecular Cancer Research Pub Date : 2024-04-08 DOI: 10.1158/1541-7786.mcr-23-1090

Vernon Justice Ebegboni, Tamara L. Jones, Tayvia Brownmiller, Patrick X. Zhao, Erica C. Pehrsson, Soumya Sundara Rajan, Natasha J. Caplen

{"title":"ETS1, a target gene of the EWSR1::FLI1 fusion oncoprotein, regulates the expression of the focal adhesion protein TENSIN3","authors":"Vernon Justice Ebegboni, Tamara L. Jones, Tayvia Brownmiller, Patrick X. Zhao, Erica C. Pehrsson, Soumya Sundara Rajan, Natasha J. Caplen","doi":"10.1158/1541-7786.mcr-23-1090","DOIUrl":"https://doi.org/10.1158/1541-7786.mcr-23-1090","url":null,"abstract":"The mechanistic basis for the metastasis of Ewing sarcomas remains poorly understood, as these tumors harbor few mutations beyond the chromosomal translocation that initiates the disease. Instead, the epigenome of Ewing sarcoma (EWS) cells reflects the regulatory state of genes associated with the DNA binding activity of the fusion oncoproteins EWSR1::FLI1 or EWSR1::ERG. In this study, we examined the EWSR1::FLI1/ERG’s repression of transcription factor genes, concentrating on those that exhibit a broader range of expression in tumors than in EWS cell lines. Focusing on one of these target genes, ETS1, we detected EWSR1::FLI1 binding and an H3K27me3 repressive mark at this locus. Depletion of EWSR1::FLI1 results in ETS1’s binding of promoter regions, substantially altering the transcriptome of EWS cells, including the upregulation of the gene encoding TENSIN3 (TNS3), a focal adhesion protein. EWS cell lines expressing ETS1 (CRISPRa) exhibited increased TNS3 expression and enhanced movement compared to control cells. Visualization of control EWS cells showed a distributed vinculin signal and a network-like organization of F-actin; in contrast, ETS1-activated EWS cells showed an accumulation of vinculin and F-actin towards the plasma membrane. Interestingly, the phenotype of ETS1-activated EWS cell lines depleted of TNS3 resembled the phenotype of the control cells. Critically, these findings have clinical relevance as TNS3 expression in EWS tumors positively correlates with that of ETS1. Implications: ETS1’s transcriptional regulation of the gene encoding the focal adhesion protein TENSIN3 in Ewing sarcoma cells promotes cell movement, a critical step in the evolution of metastasis.","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":"193 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140564808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Peritoneal Microenvironment Promotes Appendiceal Adenocarcinoma Growth: A Multi-omics Approach Using Patient-Derived Xenografts. 腹膜微环境促进阑尾腺癌生长：利用患者衍生异种移植的多组学方法。

IF 4.1 2区医学

Molecular Cancer Research Pub Date : 2024-04-02 DOI: 10.1158/1541-7786.MCR-23-0749

Vinay K Pattalachinti, Ichiaki Ito, Saikat Chowdhury, Abdelrahman Yousef, Yue Gu, Betul Beyza Gunes, Emma R Salle, Melissa W Taggart, Keith Fournier, Natalie W Fowlkes, John Paul Shen

{"title":"Peritoneal Microenvironment Promotes Appendiceal Adenocarcinoma Growth: A Multi-omics Approach Using Patient-Derived Xenografts.","authors":"Vinay K Pattalachinti, Ichiaki Ito, Saikat Chowdhury, Abdelrahman Yousef, Yue Gu, Betul Beyza Gunes, Emma R Salle, Melissa W Taggart, Keith Fournier, Natalie W Fowlkes, John Paul Shen","doi":"10.1158/1541-7786.MCR-23-0749","DOIUrl":"10.1158/1541-7786.MCR-23-0749","url":null,"abstract":"Appendiceal adenocarcinoma (AA) is unique from other gastrointestinal malignancies in that it almost exclusively metastasizes to the peritoneal cavity. However, few studies have investigated the molecular interaction of the peritoneal microenvironment and AA. Here, we use a multi-omics approach with orthotopic and flank-implanted patient-derived xenografts (PDX) to study the effect of the peritoneal microenvironment on AA. AA tumors implanted in the peritoneal microenvironment tended to grow faster and displayed greater nuclear expression of Ki-67 relative to the same tumors implanted in the flank. Comparing the tumor-specific transcriptome (excluding stromal transcription), the peritoneal microenvironment relatively upregulated genes related to proliferation, including MKI67 and EXO1. Peritoneal tumors were also enriched for proliferative gene sets, including E2F and Myc Targets. Proteomic studies found a 2.5-fold increased ratio of active-to-inactive phosphoforms of the YAP oncoprotein in peritoneal tumors, indicating downregulation of Hippo signaling.Implications: The peritoneal microenvironment promotes growth of appendiceal tumors and expression of proliferative pathways in PDXs.","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"329-336"},"PeriodicalIF":4.1,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10987270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139472739","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

AIbZIP/CREB3L4 Promotes Cell Proliferation via the SKP2-p27 Axis in Luminal Androgen Receptor Subtype Triple-Negative Breast Cancer. AIbZIP/CREB3L4通过SKP2-p27轴促进腔隙性雄激素受体亚型三阴性乳腺癌的细胞增殖

IF 4.1 2区医学

Molecular Cancer Research Pub Date : 2024-04-02 DOI: 10.1158/1541-7786.MCR-23-0629

Taichi Ito, Atsushi Saito, Yasunao Kamikawa, Nayuta Nakazawa, Kazunori Imaizumi

{"title":"AIbZIP/CREB3L4 Promotes Cell Proliferation via the SKP2-p27 Axis in Luminal Androgen Receptor Subtype Triple-Negative Breast Cancer.","authors":"Taichi Ito, Atsushi Saito, Yasunao Kamikawa, Nayuta Nakazawa, Kazunori Imaizumi","doi":"10.1158/1541-7786.MCR-23-0629","DOIUrl":"10.1158/1541-7786.MCR-23-0629","url":null,"abstract":"Breast cancer ranks first in incidence and fifth in cancer-related deaths among all types of cancer globally. Among breast cancer, triple-negative breast cancer (TNBC) has few known therapeutic targets and a poor prognosis. Therefore, new therapeutic targets and strategies against TNBC are required. We found that androgen-induced basic leucine zipper (AIbZIP), also known as cyclic AMP-responsive element-binding protein 3-like protein 4 (CREB3L4), which is encoded by Creb3l4, is highly upregulated in a particular subtype of TNBC, luminal androgen receptor (LAR) subtype. We analyzed the function of AIbZIP through depletion of AIbZIP by siRNA knockdown in LAR subtype TNBC cell lines, MFM223 and MDAMB453. In AIbZIP-depleted cells, the proliferation ratios of cells were greatly suppressed. Moreover, G1-S transition was inhibited in AIbZIP-depleted cells. We comprehensively analyzed the expression levels of proteins that regulate G1-S transition and found that p27 was specifically upregulated in AIbZIP-depleted cells. Furthermore, we identified that this p27 downregulation was caused by protein degradation modulated by the ubiquitin-proteasome system via F-box protein S-phase kinase-associated protein 2 (SKP2) upregulation. Our findings demonstrate that AIbZIP is a novel p27-SKP2 pathway-regulating factor and a potential molecule that contributes to LAR subtype TNBC progression.Implications: This research shows a new mechanism for the proliferation of LAR subtype TNBC regulated by AIbZIP, that may provide novel insight into the LAR subtype TNBC progression and the molecular mechanisms involved in cell proliferation.","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"373-385"},"PeriodicalIF":4.1,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10985479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139491345","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

NRAS Mutant Dictates AHCYL1-Governed ER Calcium Homeostasis for Melanoma Tumor Growth. NRAS 突变体决定了黑色素瘤肿瘤生长所需的 AHCYL1 控制的 ER 钙平衡。

IF 4.1 2区医学

Molecular Cancer Research Pub Date : 2024-04-02 DOI: 10.1158/1541-7786.MCR-23-0445

Chufan Cai, Jiayi Tu, Jeronimo Najarro, Rukang Zhang, Hao Fan, Freya Q Zhang, Jiacheng Li, Zhicheng Xie, Rui Su, Lei Dong, Nicole Arellano, Michele Ciboddo, Shannon E Elf, Xue Gao, Jing Chen, Rong Wu

{"title":"NRAS Mutant Dictates AHCYL1-Governed ER Calcium Homeostasis for Melanoma Tumor Growth.","authors":"Chufan Cai, Jiayi Tu, Jeronimo Najarro, Rukang Zhang, Hao Fan, Freya Q Zhang, Jiacheng Li, Zhicheng Xie, Rui Su, Lei Dong, Nicole Arellano, Michele Ciboddo, Shannon E Elf, Xue Gao, Jing Chen, Rong Wu","doi":"10.1158/1541-7786.MCR-23-0445","DOIUrl":"10.1158/1541-7786.MCR-23-0445","url":null,"abstract":"Calcium homeostasis is critical for cell proliferation, and emerging evidence shows that cancer cells exhibit altered calcium signals to fulfill their need for proliferation. However, it remains unclear whether there are oncogene-specific calcium homeostasis regulations that can expose novel therapeutic targets. Here, from RNAi screen, we report that adenosylhomocysteinase like protein 1 (AHCYL1), a suppressor of the endoplasmic reticulum (ER) calcium channel protein inositol trisphosphate receptor (IP3R), is selectively upregulated and critical for cell proliferation and tumor growth potential of human NRAS-mutated melanoma, but not for melanoma expressing BRAF V600E. Mechanistically, AHCYL1 deficiency results in decreased ER calcium levels, activates the unfolded protein response (UPR), and triggers downstream apoptosis. In addition, we show that AHCYL1 transcription is regulated by activating transcription factor 2 (ATF2) in NRAS-mutated melanoma. Our work provides evidence for oncogene-specific calcium regulations and suggests AHCYL1 as a novel therapeutic target for RAS mutant-expressing human cancers, including melanoma.Implications: Our findings suggest that targeting the AHCYL1-IP3R axis presents a novel therapeutic approach for NRAS-mutated melanomas, with potential applicability to all cancers harboring RAS mutations, such as KRAS-mutated human colorectal cancers.","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"386-401"},"PeriodicalIF":4.1,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10987265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139642586","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

Semi-Supervised, Attention-Based Deep Learning for Predicting TMPRSS2:ERG Fusion Status in Prostate Cancer Using Whole Slide Images. 利用全切片图像预测前列腺癌 TMPRSS2:ERG 融合状态的半监督式、基于注意力的深度学习技术

IF 4.1 2区医学

Molecular Cancer Research Pub Date : 2024-04-02 DOI: 10.1158/1541-7786.MCR-23-0639

Mohamed Omar, Zhuoran Xu, Sophie B Rand, Mohammad K Alexanderani, Daniela C Salles, Itzel Valencia, Edward M Schaeffer, Brian D Robinson, Tamara L Lotan, Massimo Loda, Luigi Marchionni

引用次数: 0

Retraction: Minocycline Targets the NF-κB Nexus through Suppression of TGF-β1-TAK1-IκB Signaling in Ovarian Cancer. 撤回：米诺环素通过抑制卵巢癌中的 TGF-β1-TAK1-IκB 信号，靶向 NF-κB Nexus。

IF 5.2 2区医学

Molecular Cancer Research Pub Date : 2024-04-02 DOI: 10.1158/1541-7786.MCR-24-0197

Parvin Ataie-Kachoie, Samina Badar, David L Morris, Mohammad H Pourgholami

引用次数: 0

Mass Spectrometry-Based Proteomics Identifies Serpin B9 as a Key Protein in Promoting Bone Metastases in Lung Cancer. 基于质谱的蛋白质组学发现 Serpin B9 是促进肺癌骨转移的关键蛋白。

IF 4.1 2区医学

Molecular Cancer Research Pub Date : 2024-04-02 DOI: 10.1158/1541-7786.MCR-23-0310

Yufeng Huang, Ming Gong, Hongmin Chen, Chuangzhong Deng, Xiaojun Zhu, Jiaming Lin, Anfei Huang, Yanyang Xu, Yi Tai, Guohui Song, Huaiyuan Xu, Jinxin Hu, Huixiong Feng, Qinglian Tang, Jinchang Lu, Jin Wang

{"title":"Mass Spectrometry-Based Proteomics Identifies Serpin B9 as a Key Protein in Promoting Bone Metastases in Lung Cancer.","authors":"Yufeng Huang, Ming Gong, Hongmin Chen, Chuangzhong Deng, Xiaojun Zhu, Jiaming Lin, Anfei Huang, Yanyang Xu, Yi Tai, Guohui Song, Huaiyuan Xu, Jinxin Hu, Huixiong Feng, Qinglian Tang, Jinchang Lu, Jin Wang","doi":"10.1158/1541-7786.MCR-23-0310","DOIUrl":"10.1158/1541-7786.MCR-23-0310","url":null,"abstract":"Bone metastasis (BM) is one of the most common complications of advanced cancer. Immunotherapy for bone metastasis of lung cancer (LCBM) is not so promising and the immune mechanisms are still unknown. Here, we utilized a model of BM by injecting cancer cells through caudal artery (CA) to screen out a highly bone metastatic derivative (LLC1-BM3) from a murine lung cancer cell line LLC1. Mass spectrometry-based proteomics was performed in LLC1-parental and LLC1-BM3 cells. Combining with prognostic survival information from patients with lung cancer, we identified serpin B9 (SB9) as a key factor in BM. Molecular characterization showed that SB9 overexpression was associated with poor prognosis and high bone metastatic burden in lung cancer. Moreover, SB9 could increase the ability of lung cancer cells to metastasize to the bone. The mechanistic studies revealed that tumor-derived SB9 promoted BM through an immune cell-dependent way by inactivating granzyme B, manifesting with the decreased infiltration of cytotoxic T cells and increased expression level of exhausted markers. A specific SB9-targeting inhibitor [1,3-benzoxazole-6-carboxylic acid (BTCA)] significantly suppressed LCBM in the CA mouse model. This study reveals that SB9 may serve as a therapeutic target and potential prognostic marker for patients with LCBM.Implications: SB9 as a therapeutic target for LCBM.","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"402-414"},"PeriodicalIF":4.1,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139472735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

miR-217 Regulates Normal and Tumor Cell Fate Following Induction of Endoplasmic Reticulum Stress. miR-217 在诱导内质网应激后调控正常细胞和肿瘤细胞的命运。

IF 4.1 2区医学

Molecular Cancer Research Pub Date : 2024-04-02 DOI: 10.1158/1541-7786.MCR-23-0676

Neekkan Dey, Costas Koumenis, Davide Ruggero, Serge Y Fuchs, J Alan Diehl

{"title":"miR-217 Regulates Normal and Tumor Cell Fate Following Induction of Endoplasmic Reticulum Stress.","authors":"Neekkan Dey, Costas Koumenis, Davide Ruggero, Serge Y Fuchs, J Alan Diehl","doi":"10.1158/1541-7786.MCR-23-0676","DOIUrl":"10.1158/1541-7786.MCR-23-0676","url":null,"abstract":"Rapidly proliferating cancer cells require a microenvironment where essential metabolic nutrients like glucose, oxygen, and growth factors become scarce as the tumor volume surpasses the established vascular capacity of the tissue. Limits in nutrient availability typically trigger growth arrest and/or apoptosis to prevent cellular expansion. However, tumor cells frequently co-opt cellular survival pathways thereby favoring cell survival under this environmental stress. The unfolded protein response (UPR) pathway is typically engaged by tumor cells to favor adaptation to stress. PERK, an endoplasmic reticulum (ER) protein kinase and UPR effector is activated in tumor cells and contributes tumor cell adaptation by limiting protein translation and balancing redox stress. PERK also induces miRNAs that contribute to tumor adaptation. miR-211 and miR-216b were previously identified as PERK-ATF4-regulated miRNAs that regulate cell survival. We have identified another PERK-responsive miRNA, miR-217, with increased expression under prolonged ER stress. Key targets of miR-217 are identified as TRPM1, the host gene for miR-211 and EZH2. Evidence is provided that miR-217 expression is essential for the rapid loss of miR-211 in prolonged ER stress and provides a functional link for determining whether cells adapt to stress or commit to apoptosis.Implications: PERK-dependent induction of miR-217 limits accumulation and function of the prosurvival miRNA, miR-211, to establish cell fate and promote cell commitment to apoptosis.","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"360-372"},"PeriodicalIF":4.1,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10987263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139491347","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

FGFR1 Signaling Facilitates Obesity-Driven Pulmonary Outgrowth in Metastatic Breast Cancer. 表皮生长因子受体1（FGFR1）信号传导促进了肥胖驱动的转移性乳腺癌肺部生长。

IF 4.1 2区医学

Molecular Cancer Research Pub Date : 2024-03-01 DOI: 10.1158/1541-7786.MCR-23-0955

Eylem Kulkoyluoglu Cotul, Muhammad Hassan Safdar, Sebastian Juan Paez, Aneesha Kulkarni, Mitchell G Ayers, Hang Lin, Zilin Xianyu, Dorothy Teegarden, Stephen D Hursting, Michael K Wendt

{"title":"FGFR1 Signaling Facilitates Obesity-Driven Pulmonary Outgrowth in Metastatic Breast Cancer.","authors":"Eylem Kulkoyluoglu Cotul, Muhammad Hassan Safdar, Sebastian Juan Paez, Aneesha Kulkarni, Mitchell G Ayers, Hang Lin, Zilin Xianyu, Dorothy Teegarden, Stephen D Hursting, Michael K Wendt","doi":"10.1158/1541-7786.MCR-23-0955","DOIUrl":"10.1158/1541-7786.MCR-23-0955","url":null,"abstract":"Survival of dormant, disseminated breast cancer cells contributes to tumor relapse and metastasis. Women with a body mass index greater than 35 have an increased risk of developing metastatic recurrence. Herein, we investigated the effect of diet-induced obesity (DIO) on primary tumor growth and metastatic progression using both metastatic and systemically dormant mouse models of breast cancer. This approach led to increased PT growth and pulmonary metastasis. We developed a novel protocol to induce obesity in Balb/c mice by combining dietary and hormonal interventions with a thermoneutral housing strategy. In contrast to standard housing conditions, ovariectomized Balb/c mice fed a high-fat diet under thermoneutral conditions became obese over a period of 10 weeks, resulting in a 250% gain in fat mass. Obese mice injected with the D2.OR model developed macroscopic pulmonary nodules compared with the dormant phenotype of these cells in mice fed a control diet. Analysis of the serum from obese Balb/c mice revealed increased levels of FGF2 as compared with lean mice. We demonstrate that serum from obese animals, exogenous FGF stimulation, or constitutive stimulation through autocrine and paracrine FGF2 is sufficient to break dormancy and drive pulmonary outgrowth. Blockade of FGFR signaling or specific depletion of FGFR1 prevented obesity-associated outgrowth of the D2.OR model.Implications: Overall, this study developed a novel DIO model that allowed for demonstration of FGF2:FGFR1 signaling as a key molecular mechanism connecting obesity to breakage of systemic tumor dormancy and metastatic progression.","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"254-267"},"PeriodicalIF":4.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10923021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139049063","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

LINC00869 Promotes Hepatocellular Carcinoma Metastasis via Protrusion Formation. LINC00869通过突起形成促进肝细胞癌转移。

IF 4.1 2区医学

Molecular Cancer Research Pub Date : 2024-03-01 DOI: 10.1158/1541-7786.MCR-23-0414

Xiaowen Shao, Yamei Dang, Tingting Zhang, Nan Bai, Jianing Huang, Mengya Guo, Li Sun, Minghe Li, Xiao Sun, Xinran Zhang, Feng Han, Ning Zhang, Hao Zhuang, Yongmei Li

{"title":"LINC00869 Promotes Hepatocellular Carcinoma Metastasis via Protrusion Formation.","authors":"Xiaowen Shao, Yamei Dang, Tingting Zhang, Nan Bai, Jianing Huang, Mengya Guo, Li Sun, Minghe Li, Xiao Sun, Xinran Zhang, Feng Han, Ning Zhang, Hao Zhuang, Yongmei Li","doi":"10.1158/1541-7786.MCR-23-0414","DOIUrl":"10.1158/1541-7786.MCR-23-0414","url":null,"abstract":"Coordination of filament assembly and membrane remodeling is required for the directional migration of cancer cells. The Wiskott-Aldrich syndrome protein (WASP) recruits the actin-related protein (ARP) 2/3 complex to assemble branched actin networks. The goal of our study was to assess the potential regulatory role exerted by the novel long noncoding RNA (lncRNA) LINC00869 on hepatocellular carcinoma (HCC) cells. We used HCC cells to overexpress or knockdown LINC00869, analyzed patient data from publicly available databases and Cancer Hospital Affiliated with Zhengzhou University, and used a xenograft mouse model of HCC to study the molecular mechanism associated with LINC00869 expression. We found that high levels of LINC00869 expression were associated with poor prognosis in patients with HCC. Next, we detected an interaction between LINC00869 and both WASP and ARP2 in HCC cells, and observed a modulatory effect of LINC00869 on the phosphorylation of WASP at Y291 and the activity of cell division control protein 42 (CDC42). These modulatory roles were required for WASP/CDC42 activity on F-actin polymerization to enhance membrane protrusion formation and maintain persistent cell polarization. This, in turn, promoted the migration and invasion abilities of HCC cells. Finally, we confirmed the role of LINC00869in vivo, using the tumor xenograft mouse model; and identified a positive correlation between LINC00869 expression levels and the phosphorylation levels of WASP in HCC samples. Overall, our findings suggest a unique mechanism by which LINC00869 orchestrates membrane protrusion during migration and invasion of HCC cells.Implications: LncRNA LINC00869 regulates the activity of CDC42-WASP pathway and positively affects protrusion formation in HCC cells, which expands the current understanding of lncRNA functions as well as gives a better understanding of carcinogenesis.","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"282-294"},"PeriodicalIF":4.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71484219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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