2. Academic Validation
  3. NSD2 promotes tumor angiogenesis through methylating and activating STAT3 protein

NSD2 promotes tumor angiogenesis through methylating and activating STAT3 protein

  • Oncogene. 2021 Apr;40(16):2952-2967. doi: 10.1038/s41388-021-01747-z.
Da Song 1,  Jingqin Lan 1 2,  Yaqi Chen 1,  Anyi Liu 1,  Qi Wu 1,  Chongchong Zhao 3,  Yongdong Feng 1,  Jing Wang 4,  Xuelai Luo 1,  Zhixin Cao 1,  Xiaonian Cao 1 5,  Junbo Hu 6,  Guihua Wang 7
Affiliations

Affiliations

  • 1 GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 3 Proteinomics Facility at Technology Center for Protein Sciences, Tsinghua University, Beijing, China.
  • 4 Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 5 Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 6 GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China. jbhu@tjh.tjmu.edu.cn.
  • 7 GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China. ghwang@tjh.tjmu.edu.cn.
PMID: 33742125 DOI: 10.1038/s41388-021-01747-z
Abstract

Tumor angiogenesis plays vital roles in tumorigenesis and development; regulatory mechanism of angiogenesis is still not been fully elucidated. NSD2, a Histone Methyltransferase catalyzing di-methylation of histone H3 at lysine 36, has been proved a critical molecule in proliferation, metastasis, and tumorigenesis. But its role in tumor angiogenesis remains unknown. Here we demonstrated that NSD2 promoted tumor angiogenesis in vitro and in vivo. Furthermore, we confirmed that the angiogenic function of NSD2 was mediated by STAT3. Momentously, we found that NSD2 promoted the methylation and activation of STAT3. In addition, mass spectrometry and site-directed mutagenesis assays revealed that NSD2 methylated STAT3 at lysine 163 (K163). Meanwhile, K to R mutant at K163 of STAT3 attenuated the activation and angiogenic function of STAT3. Taken together, we conclude that methylation of STAT3 catalyzed by NSD2 promotes the activation of STAT3 pathway and enhances the ability of tumor angiogenesis. Our findings investigate a NSD2-dependent methylation-phosphorylation regulation pattern of STAT3 and reveal that NSD2/STAT3/VEGFA axis might be a potential target for tumor therapy.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z