已入深夜,您辛苦了!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!祝你早点完成任务,早点休息,好梦!

Abstract 1979: JAK2/STAT3 and TrkA pathways are frequently co-activated in triple-negative and HER2-enriched breast cancers and the co-activation correlates with an increased potential of metastasis

乳腺癌 癌症研究 医学 三阴性乳腺癌 Janus激酶2 车站3 转移 癌症 酪氨酸激酶 内科学 肿瘤科 信号转导 生物 受体 生物化学
作者
Angelina T. Regua,Noah R. Aguayo,Sara Abu Jalboush,Daniel Doheny,Sara G. Manore,Dongqin Zhu,Grace L. Wong,Austin Arrigo,Calvin J. Wagner,Yang Yu,Karen Baylon,Alexandra Thomas,Michael D. Chan,Jimmy Ruiz,Guangxu Jin,Roy E. Strowd,Peiqing Sun,Linda J. Metheny‐Barlow,Jiayuh Lin,Hui‐Wen Lo
出处
期刊:Cancer Research [American Association for Cancer Research]
卷期号:81 (13_Supplement): 1979-1979
标识
DOI:10.1158/1538-7445.am2021-1979
摘要

Abstract Breast cancer is the leading cause of cancer-related deaths in American women. Despite the current standard-of-care, which implements tumor resection, radiotherapy, and chemotherapy, triple-negative and HER2-positive breast cancer patients often relapse and present with recurrent disease, for which there is no cure. Thus, there is an urgent need to identify new molecular targets to improve patient response to anti-cancer therapies. The JAK2-STAT3 and TrkA receptor tyrosine kinase signaling pathways have been separately implicated in metastatic breast cancers, but information about their crosstalk remains limited. Activated Janus kinase 2 (JAK2) receptor tyrosine kinase phosphorylates signal transducer and activator of transcription 3 (STAT3) transcription factor, inducing STAT3 nuclear translocation and transcriptional activity. Abnormal activation of STAT3-mediated transcription has been identified as a pro-tumorigenic event in breast cancers and promotes progression through induction of breast cancer stem cells, invasion, and angiogenesis. Tropomyosin receptor kinase A (TrkA) frequently forms oncogenic fusion proteins and its overexpression has been shown to drive malignant transformation of breast cancer cells. JAK2 inhibitors, while approved for treatment of myeloproliferative neoplasms, are currently in clinical trials for triple-negative breast cancers. Currently, there are two FDA-approved TrkA inhibitors for treatment of NTRK1 fusion-positive solid tumors, one of which is considered a tumor-agnostic inhibitor. However, whether these two important pathways are co-activated in breast cancers and whether the co-activation is associated with overall progression of breast cancer have not been investigated. Herein, we report that STAT3 and TrkA are more co-activated in triple-negative and HER2-enriched breast cancers, compared to luminal subtypes, as determined by immunohistochemical staining of 33 invasive breast carcinomas and datamining data of over 1,500 breast cancer patients. We also observed that high co-activation of both JAK2-STAT3 and TrkA pathways significantly shortens overall metastasis-free survival of both triple-negative and HER2-enriched breast cancer patients when compared to patients with low co-activation. Similarly, we also find that JAK2-STAT3 and TrkA co-activation also significantly shortens brain, lung, and bone metastasis-free survival in both of these breast cancer subtypes, suggesting a critical role for JAK2-STAT3 and TrkA in distant metastasis of aggressive breast cancers. Taken together, our findings indicate a novel signaling crosstalk between JAK2-STAT3 and TrkA pathways in triple-negative and HER2-enriched breast cancers, and the use of their co-activation as a prognostic indicator for metastatic breast cancers of both subtypes. Citation Format: Angelina T. Regua, Noah R. Aguayo, Sara Abu Jalboush, Daniel L. Doheny, Sara G. Manore, Dongqin Zhu, Grace L. Wong, Austin Arrigo, Calvin J. Wagner, Yang Yu, Karen Baylon, Alexandra Thomas, Michael D. Chan, Jimmy Ruiz, Guangxu Jin, Roy E. Strowd, Peiqing Sun, Linda J. Metheny-Barlow, Jiayuh Lin, Hui-Wen Lo. JAK2/STAT3 and TrkA pathways are frequently co-activated in triple-negative and HER2-enriched breast cancers and the co-activation correlates with an increased potential of metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1979.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
kk完成签到 ,获得积分10
1秒前
Polymer72应助旋转木马9个采纳,获得10
3秒前
江子川发布了新的文献求助10
3秒前
miles发布了新的文献求助30
4秒前
5秒前
7秒前
上官若男应助zfd采纳,获得10
10秒前
顾语琴发布了新的文献求助10
11秒前
Tomice发布了新的文献求助10
11秒前
Polymer72应助yhb采纳,获得10
12秒前
科研通AI2S应助五月初夏采纳,获得10
12秒前
14秒前
14秒前
随性完成签到,获得积分10
15秒前
17秒前
852应助端庄的柠檬采纳,获得10
17秒前
11完成签到,获得积分10
17秒前
17秒前
Polymer72应助陈pc采纳,获得10
17秒前
随性发布了新的文献求助10
19秒前
萧水白应助Justing采纳,获得10
20秒前
山南完成签到,获得积分10
21秒前
21秒前
c2完成签到 ,获得积分10
22秒前
安风发布了新的文献求助10
22秒前
zfd发布了新的文献求助10
23秒前
23秒前
肚皮完成签到 ,获得积分10
24秒前
24秒前
忧郁芒果完成签到,获得积分20
25秒前
完美世界应助龙骑士25采纳,获得30
25秒前
ssss完成签到,获得积分10
26秒前
30秒前
无敌OUT曼完成签到 ,获得积分10
30秒前
小马甲应助科研通管家采纳,获得10
35秒前
CipherSage应助科研通管家采纳,获得10
35秒前
asd应助科研通管家采纳,获得30
35秒前
大个应助科研通管家采纳,获得10
35秒前
所所应助科研通管家采纳,获得10
35秒前
隐形曼青应助科研通管家采纳,获得30
35秒前
高分求助中
Mantiden: Faszinierende Lauerjäger Faszinierende Lauerjäger Heßler, Claudia, Rud 1000
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 1000
Natural History of Mantodea 螳螂的自然史 1000
A Photographic Guide to Mantis of China 常见螳螂野外识别手册 800
Autoregulatory progressive resistance exercise: linear versus a velocity-based flexible model 500
Spatial Political Economy: Uneven Development and the Production of Nature in Chile 400
Research on managing groups and teams 300
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 物理化学 催化作用 细胞生物学 免疫学 冶金
热门帖子
关注 科研通微信公众号,转发送积分 3330247
求助须知:如何正确求助?哪些是违规求助? 2959843
关于积分的说明 8597367
捐赠科研通 2638376
什么是DOI,文献DOI怎么找? 1444234
科研通“疑难数据库(出版商)”最低求助积分说明 669078
邀请新用户注册赠送积分活动 656628