2. Academic Validation
  3. TUBB3 (βIII-tubulin) drives gastric cancer progression and poor prognosis by regulating cell cycle and invadopodia formation

TUBB3 (βIII-tubulin) drives gastric cancer progression and poor prognosis by regulating cell cycle and invadopodia formation

  • Cancer Biomark. 2025 Oct;42(10):18758592251390145. doi: 10.1177/18758592251390145.
Hui Ge 1,  Hui Tang 1 2,  Tingting You 1 2,  Chunmei Bai 1,  Zhao Sun 1,  Qin Han 3,  Robert Chunhua Zhao 3 4
Affiliations

Affiliations

  • 1 Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • 2 Department of Internal Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • 3 Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Beijing, China.
  • 4 School of Life Sciences, Shanghai University, Shanghai, China.
PMID: 41129675 DOI: 10.1177/18758592251390145
Abstract

BackgroundGastric Cancer is the fifth most common malignancy and third leading cause of Cancer death in China, with advanced-stage five-year survival below 20%. βIII-tubulin (TUBB3) is overexpressed in cancers but its role in gastric Cancer remains unclear.MethodsTUBB3 expression was analyzed using TCGA data and clinical samples. Knockdown models assessed its effects on proliferation, migration, and invasion in vitro and in vivo.ResultsTUBB3 was significantly upregulated in gastric Cancer tissues versus normal mucosa. High TUBB3 correlated with poorer disease-free and overall survival but not Other clinicopathological features. Functionally, TUBB3 knockdown inhibited proliferation via G2/M arrest and reduced migration/invasion by disrupting invadopodia, without affecting Apoptosis, EMT, or ECM degradation. In vivo, TUBB3 depletion suppressed tumor growth and metastasis. Mechanistically, TUBB3 promoted G2/M transition via p21/Cyclin B1 and enhanced invasiveness through Cortactin/JNK activation.ConclusionTUBB3 overexpression predicts poor prognosis in gastric Cancer. It drives proliferation via cell cycle regulation and metastasis through invadopodia formation, suggesting its potential as a therapeutic target.

Keywords

Gastric cancer; TUBB3; cell cycle; invadopodia; surivival.

Figures
Products