Increasing HER2 α2,6 sialylation facilitates gastric cancer progression and resistance via the Akt and ERK pathways

Oncology Reports
Naihua LiuShaoqiang Lin

Abstract

Upregulated β-galactoside α2,6-sialyltransferase I (ST6Gal-I) expression reportedly occurs in many cancers and is correlated with metastasis and poor prognosis. However, the mechanisms by which ST6Gal‑I facilitates gastric cancer progression remain poorly understood. Trastuzumab is exclusively used in human epidermal growth factor receptor 2 (HER2)+ gastric cancers; however, most advanced HER2+ gastric cancers develop trastuzumab resistance. Herein, we identified HER2 as an ST6Gal‑I substrate and showed that HER2 α2,6 sialylation confers protection against trastuzumab‑mediated apoptosis. SGC7901 cancer cell models in which ST6Gal‑I was overexpressed or knocked down were constructed, revealing that ST6Gal‑I overexpression induced high HER2 sialylation levels and increased cell viability and invasion compared to those in the vector cell line under serum starvation; ST6Gal‑I knockdown had the opposite effects. ST6Gal‑I overexpression also potentiated cell cycle arrest in the G2/S phase to reduce drug sensitivity. In addition, FACS analysis revealed that high ST6Gal‑I levels increased resistance to trastuzumab‑induced apoptosis, accompanied by decreased caspase‑3 levels. However, the ST6Gal‑I knockdown cell line revealed increased ...Continue Reading

Citations

Jan 26, 2020·International Journal of Molecular Sciences·Meritxell BalmañaCelso A Reis
Mar 12, 2021·Biochemical Society Transactions·Joana G RodriguesJoana Gomes

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.