Related Experiment Video

Updated: May 24, 2025

Analysis of Cell Migration within a Three-dimensional Collagen Matrix
08:02

Analysis of Cell Migration within a Three-dimensional Collagen Matrix

Published on: October 5, 2014

23.6K

ST3GAL1 regulates cancer cell migration through crosstalk between EGFR and neuropilin-1 signaling

Tan-Chi Fan1, Hui Ling Yeo1, Tsai-Hsien Hung1

  • 1Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.

The Journal of Biological Chemistry
|March 2, 2025
PubMed

Insights

The sialyltransferase ST3GAL1 promotes breast cancer metastasis by sialylating neuropilin-1 (NRP1), enhancing EGFR signaling and cell motility. Silencing ST3GAL1 inhibits migration and increases sensitivity to cetuximab.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Metastasis is a primary driver of cancer mortality.
  • Overexpression of sialyltransferase ST3GAL1 in breast cancer is linked to metastasis.
  • The precise molecular mechanisms of ST3GAL1's role in cell movement remain unclear.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which ST3GAL1 influences breast cancer cell migration.
  • To identify substrates of ST3GAL1 involved in cancer metastasis.
  • To explore ST3GAL1 as a potential therapeutic target.

Main Methods:

  • Identified neuropilin-1 (NRP1) as a substrate for ST3GAL1.
  • Analyzed gene expression data correlating ST3GAL1 and NRP1 levels with patient survival.
  • Investigated the effect of ST3GAL1-mediated sialylation on NRP1-EGFR binding affinity.
  • Assessed the impact of ST3GAL1 silencing on cell migration, wound healing, and EGF/EGFR signaling pathways.
  • Evaluated the sensitivity of cancer cells to cetuximab following ST3GAL1 silencing.

Main Results:

  • ST3GAL1 directly sialylates NRP1, increasing its binding affinity to EGFR.
  • High ST3GAL1 and NRP1 expression correlates with shorter recurrence-free and distant metastasis-free survival.
  • ST3GAL1 silencing impairs cell migration and wound healing by reducing CAPN2 activity via diminished EGF/EGFR signaling.
  • ST3GAL1 silencing enhances sensitivity to cetuximab-induced cell lysis.

Conclusions:

  • ST3GAL1 promotes tumor cell migration and metastasis through the sialylation of NRP1, enhancing EGFR signaling.
  • The ST3GAL1-NRP1-EGFR axis is a critical pathway for breast cancer cell motility.
  • ST3GAL1 represents a potential therapeutic target for inhibiting breast cancer metastasis and improving treatment efficacy.
Keywords:
EGFRNRP1ST3GAL1migrationssialylation

More Related Videos

Three-Dimensional 3D Tumor Spheroid Invasion Assay12:19

Three-Dimensional 3D Tumor Spheroid Invasion Assay

Published on: May 1, 2015

57.1K
Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion09:23

Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion

Published on: April 2, 2020

6.4K

Related Concept Videos

Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.4K
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
2.3K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.2K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.7K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K
Cytoskeletal Coordination in Cell Migration01:32

Cytoskeletal Coordination in Cell Migration

A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker...
4.7K