2. Academic Validation
  3. The Glycosyltransferase XYLT1 Activates NF-κB Signaling to Promote Metastasis of Early-Stage Lung Adenocarcinoma

The Glycosyltransferase XYLT1 Activates NF-κB Signaling to Promote Metastasis of Early-Stage Lung Adenocarcinoma

  • Cancer Res. 2025 Feb 24. doi: 10.1158/0008-5472.CAN-24-1893.
Jian Han 1,  Jianan Du 2,  Xiangmeng Li 3,  Qingbo Zhou 2,  Jiayu Zeng 2,  Jun-Tao Lin 4,  Wenle Zhou 2,  Jiayi Cai 2,  Yaokai Ye 2,  Bosui Yang 2,  Junsheng Wang 5,  Xiang Zhou 6,  Rong Lian 2,  Yi Yang 7,  Xun Zhu 7,  Hongyu Guan 8,  Liping Liu 9,  Junchao Cai 10,  Jueheng Wu 10,  Yun Li 5,  Mengfeng Li 11,  Han Tian 12
Affiliations

Affiliations

  • 1 Southern Medical University, Guangzhou, China.
  • 2 Sun Yat-sen University, China.
  • 3 Southern Medical University, China.
  • 4 Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
  • 5 Jinan University, China.
  • 6 Trauma and Hand Surgery, the First Affiliated Hospital of Sun Yat-sen University, China.
  • 7 Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
  • 8 First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
  • 9 First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
  • 10 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
  • 11 Southern Medical University, Guangzhou, Guangdong, China.
  • 12 Sun Yat-sen University, Guangzhou, China.
PMID: 39992715 DOI: 10.1158/0008-5472.CAN-24-1893
Abstract

Early-stage lung adenocarcinoma (LUAD) generally has a favorable prognosis. However, more than 30% of early-stage LUAD cases relapse within 5 years of initial treatment, even following complete removal of the primary tumor. Identification of the factors contributing to early-stage LUAD metastasis is needed to develop effective prevention and treatment strategies. Here, we found upregulation of xylosyltransferase 1 (XYLT1), a Glycosyltransferase that initiates biosynthesis of sulfated glycosaminoglycan (sGAG) chains, in metastatic recurrent lesions of early-stage LUAD, which correlated with poor prognosis. In vitro and in vivo experiments showed that XYLT1 promoted LUAD cell survival and metastasis by activating the NF-κB pathway. Mechanistically, XYLT1 interacted with IκBα and facilitated biosynthesis of sGAG-conjugated IκBα, which enhanced the interaction between IκBα and IKKs to promote proteasomal degradation of IκBα. These results illustrate that proteoglycan modification-mediated activation of NF-κB signaling is a driver of early-stage LUAD metastasis, providing a possibility for detection and intervention of early LUAD metastasis.

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