Related Experiment Video

Updated: Apr 15, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

931

Fer tyrosine kinase oligomer mediates and amplifies Src-induced tumor progression

C Oneyama1, Y Yoshikawa1, Y Ninomiya1

  • 1Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.

Oncogene
|April 14, 2015
PubMed

Insights

The Src-Fer axis, involving Fer tyrosine kinase, amplifies cancer progression by targeting ezrin. This pathway is crucial for tumorigenesis and invasiveness in cancers with upregulated c-Src.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • c-Src (a tyrosine kinase) is upregulated in many cancers, indicating its role in malignant progression.
  • The precise molecular mechanisms driving c-Src oncogenic signaling are not fully understood.
  • Previous work showed c-Src relocation to non-raft membranes promotes fibroblast transformation.

Purpose of the Study:

  • To elucidate the molecular circuits of c-Src oncogenic signaling.
  • To identify downstream targets of c-Src in non-raft membranes.
  • To investigate the role of Fer tyrosine kinase in Src-induced tumor progression.

Main Methods:

  • Identification of Fer and ezrin as non-raft c-Src targets.
  • Analysis of c-Src direct activation of Fer, including autophosphorylation and oligomerization.
  • Investigation of Fer interaction with c-Src at focal adhesion membranes.
  • Assessment of Fer's role in ezrin phosphorylation and cell transformation.
  • Evaluation of Fer's necessity for transformation induced by v-Src or EGFR activation.
  • Analysis of Fer activation's requirement for tumorigenesis and invasiveness in cancer cells.

Main Results:

  • Fer tyrosine kinase oligomers mediate and amplify Src-induced tumor progression.
  • Fer and ezrin were identified as non-raft c-Src targets.
  • c-Src directly activated Fer, leading to its autophosphorylation and amplification via Fer oligomerization.
  • Fer interacted with active c-Src at focal adhesion membranes, activating Fer-phosphorylated ezrin to induce cell transformation.
  • Fer was essential for cell transformation induced by v-Src or epidermal growth factor receptor (EGFR) activation.
  • Fer activation was required for tumorigenesis and invasiveness in c-Src-upregulated cancer cells.

Conclusions:

  • The Src-Fer axis, involving Fer tyrosine kinase and ezrin, plays a critical role in mediating and amplifying Src-induced tumor progression.
  • Fer acts as a key mediator downstream of c-Src, driving cell transformation, tumorigenesis, and invasiveness.
  • The Src-Fer axis represents a potential novel therapeutic target for a subset of human cancers characterized by c-Src upregulation.

More Related Videos

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

6.6K
Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays07:42

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays

Published on: September 19, 2018

8.4K

Related Concept Videos

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...
5.1K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

1.8K
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
21.2K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.5K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
9.4K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
7.6K