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1.
《Clinical breast cancer》2022,22(6):507-514
Breast cancer (BC) is a highly metastatic, pathological cancer that significantly affects women worldwide. The mortality rate of BC is related to its heterogeneity, aggressive phenotype, and metastasis. Recent studies have highlighted that the tumor microenvironment (TME) is critical for the interplay between metastasis mediators in BC. BC stem cells, tumor-derived exosomes, circulatory tumor cells (CTCs), and signaling pathways dynamically remodel the TME and promote metastasis. This review examines the cellular and molecular mechanisms governing the epithelial to mesenchymal transition (EMT) that facilitate metastasis. This review also discusses the role of cancer stem cells (CSCs), tumor-derived exosomes, and CTs in promoting BC metastasis. Furthermore, the review emphasizes major signaling pathways that mediate metastasis in BC. Finally, the interplay among CSCs, exosomes, and CTCs in mediating metastasis have been highlighted. Therefore, understanding the molecular cues that mediate the association of CSCs, exosomes, and CTCs in TME helps to optimize systemic therapy to target metastatic BC.  相似文献   
2.
目的探讨非小细胞肺癌(NSCLC)中miR-200a与Yes相关蛋白1(YAP1)表达量在癌组织和癌旁组织的相关性及其临床病理意义。方法回顾性选取259例非小细胞肺癌患者术后切除的肿瘤组织及癌旁组织为本次研究对象,采用RT-PCR方法检测并比较患者的miR-200a与YAP1表达量在癌组织和癌旁组织的相关性及其临床病理意义。结果所选患者中miR-200a及YAP1在非小细胞肺癌中表达量显示,miR-200a与YAP1的表达量在病理类型、浸润深度、肿瘤分级、肿瘤数目中的比较,差异无统计学意义(P>0.05)。miR-200a与YAP1的表达量在肿瘤分化程度、淋巴结转移的比较中,差异有统计学意义(P<0.05)。所选患者中miR-200a、YAP1在非小细胞肺癌组织表达量比癌旁组织较高,其中,YAP1的非小细胞肺癌组织表达量水平明显高于miR-200a的表达量水平,差异有统计学意义(P<0.05)。miR-200a、YAP1对非小细胞肺癌ROC曲线显示,miR-200a的ROC曲线下面积0.689比YAP1的0.666大,差异有统计学意义(P<0.05)。结论 miR-200a、YAP1表达量水平与非小细胞肺癌临床病理严重程度呈正相关,对非小细胞肺癌诊断有一定预测价值。  相似文献   
3.
Initially identified in Drosophila, the Hippo signaling pathway regulates how cells respond to their environment by controlling proliferation, migration and differentiation. Many recent studies have focused on characterizing Hippo pathway function and regulation in mammalian cells. Here, we present a brief overview of the major components of the Hippo pathway, as well as their regulation and function. We comprehensively review the studies that have contributed to our understanding of the Hippo pathway in the function of the peripheral nervous system and in peripheral nerve diseases. Finally, we discuss innovative approaches that aim to modulate Hippo pathway components in diseases of the peripheral nervous system.  相似文献   
4.
Cell adhesion molecule‐1 (CADM1) is a member of the immunoglobulin superfamily that functions as a tumor suppressor of lung tumors. We herein demonstrated that CADM1 interacts with Hippo pathway core kinases and enhances the phosphorylation of YAP1, and also that the membranous co–expression of CADM1 and LATS2 predicts a favorable prognosis in lung adenocarcinoma. CADM1 significantly repressed the saturation density elevated by YAP1 overexpression in NIH3T3 cells. CADM1 significantly promoted YAP1 phosphorylation on Ser 127 and downregulated YAP1 target gene expression at confluency in lung adenocarcinoma cell lines. Moreover, CADM1 was co–precipitated with multiple Hippo pathway components, including the core kinases MST1/2 and LATS1/2, suggesting the involvement of CADM1 in the regulation of the Hippo pathway through cell‐cell contact. An immunohistochemical analysis of primary lung adenocarcinomas (n = 145) revealed that the histologically low‐grade subtype frequently showed the membranous co–expression of CADM1 (20/22, 91% of low‐grade; 61/91, 67% of intermediate grade; and 13/32, 41% of high‐grade subtypes; P < 0.0001) and LATS2 (22/22, 100% of low‐grade; 44/91, 48% of intermediate‐grade; and 1/32, 3% of high‐grade subtypes; < 0.0001). A subset analysis of disease‐free survival revealed that the membranous co–expression of CADM1 and LATS2 was a favorable prognosis factor (5‐year disease‐free survival rate: 83.8%), even with nuclear YAP1‐positive expression (5‐year disease‐free survival rate: 83.7%), whereas nuclear YAP1‐positive cases with the negative expression of CADM1 and LATS2 had a poorer prognosis (5‐year disease‐free survival rate: 33.3%). These results indicate that the relationship between CADM1 and Hippo pathway core kinases at the cell membrane is important for suppressing the oncogenic role of YAP1.  相似文献   
5.
Damage accumulation in long-living macromolecules (especially extracellular matrix (ECM) proteins, nuclear pore complex (NPC) proteins, and histones) is a missing hallmark of aging. Stochastic non-enzymatic modifications of ECM trigger cellular senescence as well as many other hallmarks of aging affect organ barriers integrity and drive tissue fibrosis. The importance of it for aging makes it a key target for interventions. The most promising of them can be AGE inhibitors (chelators, O-acetyl group or transglycating activity compounds, amadorins and amadoriases), glucosepane breakers, stimulators of elastogenesis, and RAGE antagonists.  相似文献   
6.
7.
目的运用慢病毒转染技术在食管癌Eca109细胞中过表达LATS1基因,探究LATS1调控Eca109细胞增殖、凋亡及周期的作用及机制.方法构建LA TS1基因的慢病毒载体转染Eca109细胞系,RT-PCR检测细胞中LATS1mRNA的表达;Western blot检测LATS1、YAP、BAX/BCL-2的蛋白表达水平;MTS检测细胞增殖;流式细胞术检测细胞凋亡及周期;hochest33258观察细胞凋亡染色.结果 LATS1慢病毒载体转染Eca109细胞后,目的基因组(Ad-LATS1)LATS1 mRNA及LATS1蛋白表达、BAX蛋白表达明显高于对照组(CON)及阴性对照组(Ad-GFP),而YAP、BCL-2的蛋白表达明显低于对照组及Ad-GFP组(P<0.05);Ad-LATS1组Eca109细胞的增殖率从第5天开始明显低于对照组及Ad-GFP组(P<0.05);Ad-LATS1组细胞较Ad-GFP及对照组G1期比例明显增高而S期比例明显缩短,凋亡率明显增高(P<0.05),细胞荧光染色强度及范围也增高.结论 LATS1基因可上调BAX、下调YAP、BCL-2使Eca109凋亡,并诱导G1期延长、S期缩短来降低其增殖力.  相似文献   
8.
Hippo-YAP通路在机体发育和疾病发生中均具有重要作用。Hippo-YAP通路的调节紊乱可能导致病理组织过度生长和肿瘤的进展;近年来研究发现,Hippo-YAP信号通路的异常调节可能与眼部疾病相关,如圆锥角膜、Sveinsson 脉络膜视网膜萎缩和视网膜变性等,本文就Hippo/YAP 在眼部作用的研究进展进行系统综述,为眼部疾病的治疗提供理论基础。  相似文献   
9.
目的探讨FOXC1、FAT4及YAP1蛋白在上皮性卵巢癌组织表达水平及意义。方法收集了72例上皮性卵巢癌组织标本进行研究,同时选取正常卵巢组织标本60例,采用免疫组化染色法检测FOXC1、FAT4及YAP1蛋白表达。结果上皮性卵巢癌组织FOXC1蛋白阳性表达率为41.67%,明显低于正常卵巢组织(P<0.05),而FAT4蛋白阳性表达率为80.56%,YAP1为76.39%,明显高于正常卵巢组织(P<0.05);Ⅲ期、中低分化及有淋巴结转移患者FOXC1蛋白阳性表达率分别为14.29%、20.00%和18.52%,明显低于Ⅰ~Ⅱ期、高分化及无淋巴结转移患者(P<0.05);中低分化及有淋巴结转移患者FAT4、YAP1蛋白阳性表达率分别为95.00%和100.00%,90.00%和96.30%,明显高于高分化及无淋巴结转移患者(P<0.05);Ⅲ期患者YAP1蛋白阳性表达率为100.00%,明显高于Ⅰ~Ⅱ期患者(P<0.05);FOXC1蛋白与FAT4、YAP1蛋白呈负相关(γs=-0.297和-0.294,P<0.05),FAT4蛋白与YAP1蛋白呈正相关(γs=0.471,P<0.05)。结论上皮性卵巢癌组织FOXC1蛋白呈低表达,FAT4及YAP1蛋白呈高表达,三者的表达与患者临床病理特征有一定相关性,值得深入研究。  相似文献   
10.
The acquisition of chemoresistance remains a major cause of cancer mortality due to the limited accessibility of targeted or immune therapies. However, given that severe alterations of molecular features during epithelial‐to‐mesenchymal transition (EMT) lead to acquired chemoresistance, emerging studies have focused on identifying targetable drivers associated with acquired chemoresistance. Particularly, AXL, a key receptor tyrosine kinase that confers resistance against targets and chemotherapeutics, is highly expressed in mesenchymal cancer cells. However, the underlying mechanism of AXL induction in mesenchymal cancer cells is poorly understood. Our study revealed that the YAP signature, which was highly enriched in mesenchymal‐type lung cancer, was closely correlated to AXL expression in 181 lung cancer cell lines. Moreover, using isogenic lung cancer cell pairs, we also found that doxorubicin treatment induced YAP nuclear translocation in mesenchymal‐type lung cancer cells to induce AXL expression. Additionally, the concurrent activation of TGFβ signaling coordinated YAP‐dependent AXL expression through SMAD4. These data suggest that crosstalk between YAP and the TGFβ/SMAD axis upon treatment with chemotherapeutics might be a promising target to improve chemosensitivity in mesenchymal‐type lung cancer.

Abbreviations

AUC
area under the curve
AXL
AXL receptor tyrosine kinase
BCL2
B‐cell lymphoma 2
CTD2
cancer target discovery and development
CTGF
connective tissue growth factor
DEG
differentially expressed genes
DOXO
doxorubicin
EMT
epithelial–mesenchymal transition
Eto
etoposide
FDA
Food and Drug Administration
ITGB3
integrin beta‐3
MAPK
mitogen‐activated protein kinase
MMP2
matrix metalloproteinase‐2
MMP9
matrix metalloproteinase‐9
mRNA
messenger RNA
NF‐κB
nuclear factor kappa‐light‐chain‐enhancer of activated B cells
SBE
SMAD binding element
SERPINE1
serpin family E member 1
siRNA
small interfering RNA
ssGSEA
single‐sample gene set enrichment analysis
TCGA
The Cancer Genome Atlas
TGFβ
transforming growth factor beta
YAP
Yes‐associated protein
YAP8SA
mutants of inhibitory phosphorylation site at eight serine to Alanine of YAP
ZEB1
zinc finger E‐box binding homeobox 1
ZEB2
zinc finger E‐box‐binding homeobox 2
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