TGFβ promotes YAP‐dependent AXL induction in mesenchymal‐type lung cancer cells

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

     

扶正消瘤颗粒对原发性肝癌血清中VEGF、HIF-1α表达的影响及临床意义＊

目的 探讨扶正消瘤颗粒对原发性肝癌血清中血管内皮生长因子（Vascular endothelial growth factor，VEGF）和缺氧诱导因子-1α（Hypoxia inducible factor-1α，HIF-1α）表达的影响及临床意义。方法 选择符合纳入标准的原发性肝癌患者66例，按1∶1随机分试验组和对照组。观察治疗过程中两组VEGF、HIF-1α水平的变化及对患者临床疗效指标的影响。结果 （1）在性别、年龄、合并乙型肝炎、Child-Pugh分级、AFP值、临床分期方面，试验组和对照组差异无统计学意义（P > 0.05）。（2）肝癌患者在治疗各时间节点的VEGF和HIF-1α表达水平呈线性正相关（r = 0.829，P < 0.001）。（3）VEGF浓度在经导管动脉化疗栓塞术（Transcatheter arterial chemoembolization，TACE）后3月降至术前水平（P > 0.05），HIF-1α在TACE后3月仍高于术前（P < 0.05）。（4）扶正消瘤颗粒可降低HIF-1α水平，下调VEGF的表达。（5）扶正消瘤颗粒可减少TACE序贯RFA治疗后的不良反应，提高患者的生活质量（P < 0.05）。（6）血清中VEGF水平与生活质量无明显相关性（P > 0.05，r = 0.251），HIF-1α水平与生活质量存在正相关性（P < 0.05，r = 0.450）。结论 扶正消瘤颗粒可明显改善TACE序贯RFA治疗后患者生活质量，降低HIF-1α水平，下调VEGF的表达，抑制肿瘤血管生成。     

国际内镜疝学会腹壁疝和切口疝腹腔镜治疗指南更新解读（六）

<正>第5章术前辅助措施在腹疝修补术中的作用通过Medline、PubMed、Cochrane Library以及相关期刊和参考文献进行了系统的文献检索,证据结论:(1)在腹壁疝修补术之前使用A型肉毒素(botulinum toxin type A,BTA)与阿片类镇痛的使用显著减少疼痛。证据级别:3级。(2)(1)应用BTA可使腹壁疝直径减小,腹壁外侧肌厚度显著减少,腹壁外侧肌显著延长。在大多数腹疝患者中,单独     

WNT10A variants: following the pattern of inheritance in tooth agenesis and self-reported family history of cancer

Clinical Oral Investigations - The aim of this study was the analysis of WNT10A variants in seven families of probands with various forms of tooth agenesis and self-reported family history of...