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Updated: Jul 4, 2026

Spontaneous Murine Model of Anaplastic Thyroid Cancer
05:39

Spontaneous Murine Model of Anaplastic Thyroid Cancer

Published on: February 3, 2023

ANXA2+ Small Extracellular Vesicles Drive Chemoresistance in Anaplastic Thyroid Cancer by Promoting XRCC5 Lactylation

Shanshan Su1, YiShan Xiong1, Yuxuan Liang1

  • 1Jiangxi Otorhinolaryngology-Head and Neck Surgery Institute, Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|July 3, 2026
PubMed

Insights

Anaplastic thyroid carcinoma cells resist cisplatin via small extracellular vesicles (sEVs) that enhance DNA repair through protein lactylation. Targeting this ANXA2+ sEV/lactylation pathway can overcome chemoresistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Anaplastic thyroid carcinoma (ATC) exhibits extreme aggression and poor survival rates.
  • Intrinsic cisplatin resistance is a major challenge in treating ATC.

Purpose of the Study:

  • To identify novel mechanisms of chemoresistance in ATC.
  • To investigate the role of small extracellular vesicles (sEVs) and protein lactylation in cisplatin resistance.

Main Methods:

  • Analysis of sEVs secreted by ATC cells, focusing on protein content.
  • Investigating the interaction between Annexin A2 (ANXA2), SRC kinase, and lactate dehydrogenase A (LDHA).
  • Assessing the impact of lactate production and lysine lactylation on DNA repair pathways, specifically non-homologous end-joining (NHEJ).

Main Results:

  • ATC-derived sEVs contain ANXA2, which promotes LDHA phosphorylation and lactate production.
  • Lactate fuels lysine lactylation of Ku80 (XRCC5) at K265, enhancing NHEJ pathway efficiency.
  • This lactylation axis (ANXA2+ sEV/SRC/LDHA/lactate/XRCC5) promotes rapid repair of cisplatin-induced DNA damage, conferring chemoresistance.

Conclusions:

  • A novel mechanism involving ANXA2+ sEVs, SRC/LDHA signaling, and XRCC5 lactylation drives NHEJ-mediated chemoresistance in ATC.
  • Targeting the ANXA2+ sEV/lactylation axis or inhibiting LDHA can sensitize ATC to cisplatin.
  • This study reveals potential therapeutic strategies for overcoming cisplatin resistance in anaplastic thyroid carcinoma.
Keywords:
XRCC5anaplastic thyroid carcinomalactylationnon‐homologous end‐joining repairsmall extracellular vesicle

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