Experimental cell research最新文献_第10页

Live-cell imaging and CLEM reveal the existence of ACTN4-dependent ruffle-edge lamellipodia acting as a novel mode of cell migration 活细胞成像和 CLEM 揭示了 ACTN4 依赖性皱边薄片的存在，它是一种新型的细胞迁移模式。

IF 3.3 3区生物学

Experimental cell research Pub Date : 2024-09-01 DOI: 10.1016/j.yexcr.2024.114232

Haruka Morishita , Katsuhisa Kawai , Youhei Egami , Kazufumi Honda , Nobukazu Araki

{"title":"Live-cell imaging and CLEM reveal the existence of ACTN4-dependent ruffle-edge lamellipodia acting as a novel mode of cell migration","authors":"Haruka Morishita , Katsuhisa Kawai , Youhei Egami , Kazufumi Honda , Nobukazu Araki","doi":"10.1016/j.yexcr.2024.114232","DOIUrl":"10.1016/j.yexcr.2024.114232","url":null,"abstract":"<div><p>α-Actinin-4 (ACTN4) expression levels are correlated with the invasive and metastatic potential of cancer cells; however, the underlying mechanism remains unclear. Here, we identified ACTN4-localized ruffle-edge lamellipodia using live-cell imaging and correlative light and electron microscopy (CLEM). BSC-1 cells expressing EGFP-ACTN4 showed that ACTN4 was most abundant in the leading edges of lamellipodia, although it was also present in stress fibers and focal adhesions. ACTN4 localization in lamellipodia was markedly diminished by phosphoinositide 3-kinase inhibition, whereas its localization in stress fibers and focal adhesions remained. Furthermore, overexpression of ACTN4, but not ACTN1, promoted lamellipodial formation. Live-cell analysis demonstrated that ACTN4-enriched lamellipodia are highly dynamic and associated with cell migration. CLEM revealed that ACTN4-enriched lamellipodia exhibit a characteristic morphology of multilayered ruffle-edges that differs from canonical flat lamellipodia. Similar ruffle-edge lamellipodia were observed in A549 and MDA-MB-231 invasive cancer cells. ACTN4 knockdown suppressed the formation of ruffle-edge lamellipodia and cell migration during wound healing in A549 monolayer cultures. Additionally, membrane-type 1 matrix metalloproteinase was observed in the membrane ruffles, suggesting that ruffle-edge lamellipodia have the ability to degrade the extracellular matrix and may contribute to active cell migration/invasion in certain cancer cell types.</p></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114232"},"PeriodicalIF":3.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of TET2-mediated methylation reconstruction on A2058 melanoma cell sensitivity to matrix stiffness in a 3D culture system 在三维培养系统中，TET2 介导的甲基化重构对 A2058 黑色素瘤细胞对基质硬度敏感性的影响。

IF 3.3 3区生物学

Experimental cell research Pub Date : 2024-09-01 DOI: 10.1016/j.yexcr.2024.114224

Zhizhong Shen , Zixian Liu , Meng Li , Lu Han , Jianming Wang , Xunwei Wu , Shengbo Sang

{"title":"Effects of TET2-mediated methylation reconstruction on A2058 melanoma cell sensitivity to matrix stiffness in a 3D culture system","authors":"Zhizhong Shen , Zixian Liu , Meng Li , Lu Han , Jianming Wang , Xunwei Wu , Shengbo Sang","doi":"10.1016/j.yexcr.2024.114224","DOIUrl":"10.1016/j.yexcr.2024.114224","url":null,"abstract":"<div><p>Matrix stiffness is a crucial factor in the tumor microenvironment, impacting tumor progression and development. TET2 is vital for epigenetic regulation in melanoma and is significantly reduced in advanced melanomas compared with nevi and thin melanomas. However, it is unclear how TET2 mediates the effect of matrix stiffness on melanoma cells. This study utilized A2058 cell lines and prepared different stiffness collagen hydrogels to evaluate TET2 overexpression (TET2OE) and mutant (TET2M) melanoma cells' activity, proliferation, and invasion. A2058 melanoma cells' viability and invasion decreased with increased matrix stiffness, with TET2OE cells experiencing a more significant impact than TET2M cells. Methylation analysis revealed that TET2 determines gene methylation levels, influencing cell-ECM interactions. Transcriptome analysis confirmed that TET2 promotes matrix stiffness's effect on melanoma cell fate. This research provides promising directions and opportunities for melanoma treatment.</p></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 1","pages":"Article 114224"},"PeriodicalIF":3.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Overexpression of DUSP26 gene suppressed the proliferation, migration, and invasion of human prostate cancer cells 过表达 DUSP26 基因可抑制人类前列腺癌细胞的增殖、迁移和侵袭。

IF 3.3 3区生物学

Experimental cell research Pub Date : 2024-08-31 DOI: 10.1016/j.yexcr.2024.114231

Ruo-Hui Huang , Qing-Ming Zeng , Bo Jiang , Gang Xu , Guan-Cheng Xiao , Wei Xia , Yun-Feng Liao , Yu-Ting Wu , Jun-Rong Zou , Biao Qian , Ri-Hai Xiao , Yuan-Hu Yuan , Guo-Xi Zhang , Xiao-Feng Zou

{"title":"Overexpression of DUSP26 gene suppressed the proliferation, migration, and invasion of human prostate cancer cells","authors":"Ruo-Hui Huang , Qing-Ming Zeng , Bo Jiang , Gang Xu , Guan-Cheng Xiao , Wei Xia , Yun-Feng Liao , Yu-Ting Wu , Jun-Rong Zou , Biao Qian , Ri-Hai Xiao , Yuan-Hu Yuan , Guo-Xi Zhang , Xiao-Feng Zou","doi":"10.1016/j.yexcr.2024.114231","DOIUrl":"10.1016/j.yexcr.2024.114231","url":null,"abstract":"<div><p>Prostate cancer (PCa) is threatening the health of millions of people, the pathological mechanism of prostate cancer has not been fully elaborated, and needs to be further explored. Here, we found that the expression of DUSP26 is dramatically suppressed, and a positive connection of its expression with PCa prognosis was also observed. In vitro, overexpression of DUSP26 significantly inhibited the proliferative, migrative, and invasive capacities of PC3 cells, DUSP26 silencing presented opposite results. Tumor formation experiments in subcutaneous nude mice demonstrated that DUSP26 overexpression could significantly suppress PC3 growth <em>in vivo</em>. Moreover, the mechanism of DUSP26 gene and PCa was discovered by RNA-Seq analysis. We found that DUSP26 significantly inhibited MAPK signaling pathway activation, and further experiments displayed that DUSP26 could impair TAK1, p38, and JNK phosphorylation. Interestingly, treatment with the TAK1 inhibitor (iTAK1) attenuated the effect of DUSP26 on PC3 cells. Together, these results suggested that DUSP26 may serve as a novel therapeutic target for PC3 cell type PCa, the underlying mechanism may be through TAK1-JNK/p38 signaling.</p></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114231"},"PeriodicalIF":3.3,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enzymatic activity of fibroblast activation protein-α is essential for TGF-β1-induced fibroblastic differentiation of human periodontal ligament cells 成纤维细胞活化蛋白-α的酶活性对 TGF-β1 诱导的人类牙周韧带细胞成纤维细胞分化至关重要。

IF 3.3 3区生物学

Experimental cell research Pub Date : 2024-08-31 DOI: 10.1016/j.yexcr.2024.114230

Seong-Min Kim , Young-Joo Jang

{"title":"Enzymatic activity of fibroblast activation protein-α is essential for TGF-β1-induced fibroblastic differentiation of human periodontal ligament cells","authors":"Seong-Min Kim , Young-Joo Jang","doi":"10.1016/j.yexcr.2024.114230","DOIUrl":"10.1016/j.yexcr.2024.114230","url":null,"abstract":"<div><p>Human periodontal ligament cells (hPDLCs) contain multipotent postnatal stem cells that can differentiate into PDL fibroblasts, osteoblasts, and cementoblasts. Interaction between the extracellular environment and stem cells is an important factor for differentiation into other progenitor cells. To identify cell surface molecules that induce PDL fibroblastic differentiation, we developed a series of monoclonal antibodies against membrane/ECM molecules. One of these antibodies, an anti-PDL25 antibody, recognizes approximately a 100 kDa protein, and this antigenic molecule accumulates in the periodontal ligament region of tooth roots. By mass spectrometric analysis, we found that the antigenic molecule recognized by the anti-PDL25 antibody is fibroblast activation protein α (FAPα). The expression level of FAPα/PDL25 increased in TGF-β1-induced PDL fibroblasts, and this protein was localized in the cell boundaries and elongated processes of the fibroblastic cells. Ectopic expression of FAPα induced fibroblastic differentiation. In contrast, expression of representative markers for PDL differentiation was decreased by knock down and antibody blocking of FAPα/PDL25. Inhibition of dipeptidyl peptidase activity by a potent FAPα inhibitor dramatically inhibited PDL fibroblastic marker expression but did not affect in cell proliferation and migration.</p></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114230"},"PeriodicalIF":3.3,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014482724003215/pdfft?md5=d5747d1262383979d15b50a3ab55dd17&pid=1-s2.0-S0014482724003215-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Directed differentiation of human embryonic stem cells into conjunctival epithelial cells 将人类胚胎干细胞定向分化为结膜上皮细胞。

IF 3.3 3区生物学

Experimental cell research Pub Date : 2024-08-30 DOI: 10.1016/j.yexcr.2024.114227

Xiangyue Hu , Chunxiao Dong , Dulei Zou , Chao Wei , Yani Wang , Zongren Li , Haoyun Duan , Zongyi Li

{"title":"Directed differentiation of human embryonic stem cells into conjunctival epithelial cells","authors":"Xiangyue Hu , Chunxiao Dong , Dulei Zou , Chao Wei , Yani Wang , Zongren Li , Haoyun Duan , Zongyi Li","doi":"10.1016/j.yexcr.2024.114227","DOIUrl":"10.1016/j.yexcr.2024.114227","url":null,"abstract":"<div><p>Severe conjunctival damage can lead to extensive ocular cicatrisation, fornix shortening, and even ocular surface failure, resulting in significant vision impairment. Conjunctival reconstruction is the primary therapeutic strategy for these clinical conjunctival diseases. However, there have been limited studies on induced differentiation of conjunctival epithelial cells derived from stem cells. In this study, we established a chemical defined differentiation protocol from human embryonic stem cells (hESCs) into conjunctival epithelial cells. hES cell line H1 was used for differentiation, and RT-qPCR, immunofluorescence staining, Periodic-acid-Schiff staining (PAS), and transcriptome analysis were employed to identify the differentiated cells. Here, to imitate the development of the vertebrate conjunctiva, hESCs were induced using a three-step process involving first chetomin was used to induce ocular surface ectoderm, then nicotinamide was used to induce ocular surface epithelial progenitor cells, and finally epidermal growth factor, keratinocyte growth factor and other factors were used to differentiate mature conjunctival epithelial cells. hESC-derived conjunctival epithelial cells expressed mature conjunctival epithelial lineage markers (including PAX6, P63, K13). The presence of goblet cells was confirmed by positive PAS. Transcriptome analysis revealed that hESC-derived conjunctival epithelial cells possessed a more naïve phenotype, and exhibited greater proliferation capacity compared to mature human conjunctival epithelial cells, suggesting their potential as alternative seed cells for conjunctival reconstruction.</p></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114227"},"PeriodicalIF":3.3,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of gasotransmitters in necroptosis 气体递质在坏死中的作用

IF 3.3 3区生物学

Experimental cell research Pub Date : 2024-08-30 DOI: 10.1016/j.yexcr.2024.114233

Lei Cao , Xue-Li Wang , Ti Chu , Yan-Wen Wang , Yong-Qi Fan , Yu-Hang Chen , Yi-Wen Zhu , Jing Zhang , Xin-Ying Ji , Dong-Dong Wu

引用次数: 0

Sensitivity of triple negative breast cancer cells to ATM-dependent ferroptosis induced by sodium selenite 三阴性乳腺癌细胞对亚硒酸钠诱导的 ATM 依赖性铁猝灭的敏感性

IF 3.3 3区生物学

Experimental cell research Pub Date : 2024-08-29 DOI: 10.1016/j.yexcr.2024.114222

Mengchen Xu , Xu Gao , Lu Yue , Jinyu Li , Xiaoya Feng , Dejun Huang , Hui Cai , Yongmei Qi

{"title":"Sensitivity of triple negative breast cancer cells to ATM-dependent ferroptosis induced by sodium selenite","authors":"Mengchen Xu , Xu Gao , Lu Yue , Jinyu Li , Xiaoya Feng , Dejun Huang , Hui Cai , Yongmei Qi","doi":"10.1016/j.yexcr.2024.114222","DOIUrl":"10.1016/j.yexcr.2024.114222","url":null,"abstract":"<div><p>Targeting ferroptosis, a type of cell death elicited by Fe<sup>2+</sup> and lipid reactive oxygen species (L-ROS), provides a novel strategy for cancer therapy. Selenium has the potential to treat cancers by acting as a pro-oxidative agent, thus leading to cancer cell death. Here, we found that the triple negative breast cancer (TNBC) MDA-MB-231 cells were more sensitive to ferroptosis induced by sodium selenite (Na<sub>2</sub>SeO<sub>3</sub>) than that of non-TNBC MCF-7 cells. Na<sub>2</sub>SeO<sub>3</sub> significantly elevated the level of L-ROS, MDA and Fe<sup>2+</sup>, decreased the content of GSH and the enzyme activity of GPx, disrupted the expression of ferroptosis related proteins such as GPx4 and FTH1, as well as compromised mitochondrial morphology in MDA-MB-231 cells. Moreover, ATM was activated by Na<sub>2</sub>SeO<sub>3</sub> in MDA-MB-231 cells. Notably, Na<sub>2</sub>SeO<sub>3</sub>-induced ferroptosis was inhibited by ATM kinase inhibitor KU55933 or siATM, suggesting that Na<sub>2</sub>SeO<sub>3</sub>-induced ferroptosis was mediated by ATM protein in MDA-MB-231 cells. Our findings suggest a therapeutic strategy by ferroptosis against TNBC and deepened our understanding of ATM function.</p></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114222"},"PeriodicalIF":3.3,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RNA-seq transcriptomic profiling of TGF-β2-exposed human trabecular meshwork explants: Advancing insights beyond conventional cell culture models 暴露于 TGF-β2 的人类小梁网外植体的 RNA-Seq 转录组分析：超越传统细胞培养模型的新见解。

IF 3.3 3区生物学

Experimental cell research Pub Date : 2024-08-28 DOI: 10.1016/j.yexcr.2024.114220

J. Buffault , É. Reboussin , F. Blond , X. Guillonneau , P. Bastelica , K. Kessal , M. Akkurt Arslan , S. Melik-Parsadaniantz , A. Réaux-le Goazigo , A. Labbé , F. Brignole-Baudouin , C. Baudouin

{"title":"RNA-seq transcriptomic profiling of TGF-β2-exposed human trabecular meshwork explants: Advancing insights beyond conventional cell culture models","authors":"J. Buffault , É. Reboussin , F. Blond , X. Guillonneau , P. Bastelica , K. Kessal , M. Akkurt Arslan , S. Melik-Parsadaniantz , A. Réaux-le Goazigo , A. Labbé , F. Brignole-Baudouin , C. Baudouin","doi":"10.1016/j.yexcr.2024.114220","DOIUrl":"10.1016/j.yexcr.2024.114220","url":null,"abstract":"<div><p>Primary open-angle glaucoma (POAG), a leading cause of irreversible vision loss, is closely linked to increased intraocular pressure (IOP), with the trabecular meshwork (TM) playing a critical role in its regulation. The TM, located at the iridocorneal angle, acts as a sieve, filtering the aqueous humor from the eye into the collecting ducts, thus maintaining proper IOP levels. The transforming growth factor-beta 2 (TGF-β2) signaling pathway has been implicated in the pathophysiology of primary open-angle glaucoma POAG particularly, in the dysfunction of the TM. This study utilizes human TM explants to closely mimic <em>in vivo</em> conditions, thereby minimizing transcriptional changes that could arise from cell culture enabling an exploration of the transcriptomic impacts of TGF-β2. Through bulk RNA sequencing and immunohistological analysis, we identified distinct gene expression patterns and morphological changes induced by TGF-β2 exposure (5 ng/ml for 48 h). Bulk RNA sequencing identified significant upregulation in genes linked to extracellular matrix (ECM) regulation and fibrotic signaling. Immunohistological analysis further elucidated the morphological alterations, including cytoskeletal rearrangements and ECM deposition, providing a visual confirmation of the transcriptomic data. Notably, the enrichment analysis unveils TGF-β2’s influence on both bone morphogenic protein (BMP) and Wnt signaling pathways, suggesting a complex interplay of molecular mechanisms contributing to TM dysfunction in glaucoma. This characterization of the transcriptomic modifications on an explant model of TM obtained under the effect of this profibrotic cytokine involved in glaucoma is crucial in order to develop and test new molecules that can block their signaling pathways.</p></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114220"},"PeriodicalIF":3.3,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

N6-methyladenosine modification of linc-OIP5 confers paclitaxel resistance in breast cancer through a DDX5-dependent mechanism Linc-OIP5的N6-甲基腺苷修饰通过DDX5依赖性机制赋予乳腺癌紫杉醇抗性。

IF 3.3 3区生物学

Experimental cell research Pub Date : 2024-08-28 DOI: 10.1016/j.yexcr.2024.114226

Xuedong Wang , Ping Li , Ziyun Zhang , Xinping Wang , Qiwei Jian , Yueping Wang

{"title":"N6-methyladenosine modification of linc-OIP5 confers paclitaxel resistance in breast cancer through a DDX5-dependent mechanism","authors":"Xuedong Wang , Ping Li , Ziyun Zhang , Xinping Wang , Qiwei Jian , Yueping Wang","doi":"10.1016/j.yexcr.2024.114226","DOIUrl":"10.1016/j.yexcr.2024.114226","url":null,"abstract":"<div><div>Chemoresistance is a significant obstacle in the treatment of breast cancer (BC). Due to its diverse composition, the causes of chemoresistance in BC are complex and have not been completely understood. In this article, we explored the mechanism of N6-methyladenosine (m6A)-modified long intervening noncoding RNA (linc)-OIP5 in BC chemoresistance. We successfully constructed drug-resistant cell lines MCF-7/P and MDA-MB-231/P by exposing parental MDA-MB-231 and MCF-7 cells to escalating doses of paclitaxel (PTX) and revealed multiple m6A methylation modification sites on linc-OIP5 according to the predictive analysis of the SRAMP database. Linc-OIP5 expression and m6A modification were up-regulated in PTX-resistant BC cells. Inhibition of m6A modification or linc-OIP5 knockdown facilitated PTX-resistant and parental BC cell apoptosis and repressed proliferation and migration. Mechanistically, linc-OIP5 bound to TRIM5 and reduced the ubiquitination of DDX5, thus stabilizing the DDX5 protein. Additionally, DDX5 overexpression partly abrogated the suppressing effects of inhibited m6A modification or si-linc-OIP5 on cell proliferation, migration and PTX resistance. These findings indicate that m6A-modified linc-OIP5 reduced DDX5 ubiquitination and enhanced DDX5 stability by binding to TRIM5, thereby promoting BC cell proliferation, migration and PTX resistance, and inhibiting apoptosis.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114226"},"PeriodicalIF":3.3,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Leptin and insulin synergize with PIK3CA mutation to enhance PD-L1 mediated immunosuppression in thyroid cancer 瘦素和胰岛素与PIK3CA突变协同作用，增强甲状腺癌中PD-L1介导的免疫抑制。

IF 3.3 3区生物学

Experimental cell research Pub Date : 2024-08-27 DOI: 10.1016/j.yexcr.2024.114229

Kainan Wu , Yuerong Chen , Runsheng Guo , Qingtan Zeng , Yue Yu

{"title":"Leptin and insulin synergize with PIK3CA mutation to enhance PD-L1 mediated immunosuppression in thyroid cancer","authors":"Kainan Wu , Yuerong Chen , Runsheng Guo , Qingtan Zeng , Yue Yu","doi":"10.1016/j.yexcr.2024.114229","DOIUrl":"10.1016/j.yexcr.2024.114229","url":null,"abstract":"<div><p>The incidence of thyroid cancer keeps rising and obesity emerges as an important risk factor for thyroid cancer, but the underlying mechanism is far from clear. Here, we hypothesize that leptin and insulin, two hormones closely related to obesity, may contribute to the pathogenesis of thyroid cancer. By using a combination of assays like CRISPR KO, cancer cell-T cell co-culture, ApoLive-Glo™ multiplex assay and syngeneic mouse model, we show that PD-L1 protein levels are increased dose-dependently by leptin or insulin in multiple thyroid cancer cell lines. Leptin and insulin converge to activate the PI3K-AKT pathway to enhance PD-L1 expression and activity. In addition, we use CRISPR KO to generate human thyroid cancer cells expressing WT PIK3CA or PIK3CA-E545K mutant. PIK3CA- E545K mutation makes the thyroid cancer cells to produce more PD-L1 protein upon leptin or insulin treatment. Thus, leptin and insulin synergize with PIK3CA mutation to enhance PD-L1 expression. Dual blockade of leptin and insulin signaling pathways reduces tumor size in a syngeneic mouse model. Our study suggests that understanding the interaction between genetic mutation and obesity is crucial for comprehensively assessing thyroid cancer risk and developing effective treatment strategies.</p></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"442 2","pages":"Article 114229"},"PeriodicalIF":3.3,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0