Surreal illustration of cancer cells and signaling pathways with fusion protein hijacking a pathway.

Decoding Cancer: How Fusion Proteins Hijack Growth Signals for Survival

Nico Varela in Health & Wellness December 2025 • 4 min read.

"Unraveling the Connection Between Oncogenic Fusion Proteins and the Insulin-Like Growth Factor Pathway in Cancer"

Cancer, a disease characterized by uncontrolled cell growth, often arises from genetic mutations that disrupt normal cellular functions. Among these mutations, chromosomal translocations, where parts of chromosomes break off and attach to other chromosomes, play a significant role. These translocations can lead to the creation of 'fusion proteins,' abnormal proteins that drive cancer development by interfering with normal signaling pathways.

One critical signaling pathway that cancer cells frequently exploit is the insulin-like growth factor (IGF) pathway. The IGF pathway regulates cell growth, survival, and metabolism, making it an attractive target for cancer cells seeking to gain an advantage. The IGF1R receptor, a key component of this pathway, promotes cell survival and proliferation when activated by IGF ligands.

Recent research has shed light on how oncogenic fusion proteins manipulate the IGF pathway to promote cancer progression. By increasing IGF1R levels and activity, these fusion proteins can drive uncontrolled cell growth and prevent cell death, ultimately contributing to tumor formation and metastasis. Understanding this intricate relationship between fusion proteins and the IGF pathway is crucial for developing more effective cancer therapies.

How Fusion Proteins Highjack the IGF Signaling Pathway?

Surreal illustration of cancer cells and signaling pathways with fusion protein hijacking a pathway.

Oncogenic fusion proteins often disrupt the normal function of transcription factors, proteins that regulate gene expression. These disrupted transcription factors can then activate the IGF1R gene, leading to increased IGF1R production. This overproduction of IGF1R makes cancer cells more sensitive to IGF ligands, further stimulating cell growth and survival.

Several mechanisms contribute to the aberrant activation of the IGF pathway by fusion proteins:

Increased IGF1R Expression: Fusion proteins can directly activate the IGF1R gene, leading to higher levels of the receptor on the cell surface.
Ligand-Mediated Receptor Phosphorylation: Increased IGF1R levels enhance the receptor's response to IGF ligands, resulting in increased receptor phosphorylation and downstream signaling.
Adoption of the IGF1R Signaling Pathway: Fusion proteins can hijack the IGF1R signaling pathway, using it to transmit growth and survival signals even in the absence of IGF ligands.

This 'adoption' of the IGF pathway allows cancer cells to bypass normal regulatory mechanisms and proliferate uncontrollably. For example, the TMPRSS2-ERG fusion protein, common in prostate cancer, increases IGF1R expression, leading to enhanced cell growth and survival. Similarly, the ETV6-NTRK3 fusion protein, found in some pediatric cancers, forms a complex with IGF1R, further driving its activation.

Targeting the Source: Future Therapies

The discovery of how oncogenic fusion proteins exploit the IGF pathway opens new avenues for targeted cancer therapies. By simultaneously targeting both the fusion proteins and the IGF1R receptor, researchers hope to develop more effective treatments that can overcome the limitations of existing therapies. This combined approach could potentially disrupt the aberrant signaling pathways driving cancer growth, leading to improved outcomes for patients.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1186/s12943-018-0807-z, Alternate LINK

Title: Oncogenic Fusion Proteins Adopt The Insulin-Like Growth Factor Signaling Pathway

Subject: Cancer Research

Journal: Molecular Cancer

Publisher: Springer Science and Business Media LLC

Authors: Haim Werner, Shilhav Meisel-Sharon, Ilan Bruchim

Published: 2018-02-19

Everything You Need To Know

What are fusion proteins, and how do they contribute to cancer development?

Fusion proteins are abnormal proteins created when chromosomal translocations occur, causing parts of chromosomes to break off and attach to other chromosomes. These proteins can disrupt normal signaling pathways, such as the Insulin-Like Growth Factor pathway, leading to uncontrolled cell growth and cancer development. For example, the TMPRSS2-ERG fusion protein, found in prostate cancer, increases IGF1R expression, leading to enhanced cell growth and survival. Similarly, the ETV6-NTRK3 fusion protein, found in some pediatric cancers, forms a complex with IGF1R, further driving its activation.

How does the Insulin-Like Growth Factor (IGF) pathway normally function, and why is it important in cancer?

The Insulin-Like Growth Factor (IGF) pathway regulates cell growth, survival, and metabolism. The IGF1R receptor, a key component of this pathway, promotes cell survival and proliferation when activated by IGF ligands. Cancer cells exploit this pathway to gain a growth advantage. By manipulating the IGF pathway, cancer cells can increase IGF1R levels and activity, driving uncontrolled cell growth and preventing cell death, ultimately leading to tumor formation and metastasis.

In what specific ways do oncogenic fusion proteins manipulate the IGF signaling pathway to promote cancer progression?

Oncogenic fusion proteins manipulate the IGF pathway through several mechanisms. First, they can directly activate the IGF1R gene, leading to higher levels of the IGF1R receptor on the cell surface. Second, increased IGF1R levels enhance the receptor's response to IGF ligands, resulting in increased receptor phosphorylation and downstream signaling. Finally, fusion proteins can hijack the IGF1R signaling pathway, using it to transmit growth and survival signals even in the absence of IGF ligands. For instance, the TMPRSS2-ERG fusion protein, common in prostate cancer, increases IGF1R expression, leading to enhanced cell growth and survival.

What therapeutic strategies are being explored to target the interaction between fusion proteins and the IGF1R receptor in cancer cells?

Researchers are exploring targeted cancer therapies that simultaneously target both the fusion proteins and the IGF1R receptor. This combined approach aims to disrupt the aberrant signaling pathways driving cancer growth, leading to improved outcomes for patients. By targeting the source (fusion proteins) and a key component of the hijacked pathway (IGF1R), it is hoped to overcome the limitations of existing therapies that may only address one aspect of the dysregulated signaling.

How does increased IGF1R expression contribute to the aggressiveness of cancer, and what role do fusion proteins play in this process?

Increased IGF1R expression makes cancer cells more sensitive to IGF ligands, leading to enhanced cell growth and survival. Fusion proteins play a crucial role by directly activating the IGF1R gene, leading to higher levels of the receptor on the cell surface. This overproduction of IGF1R allows cancer cells to bypass normal regulatory mechanisms and proliferate uncontrollably, driving tumor formation and metastasis. For example, the TMPRSS2-ERG fusion protein increases IGF1R expression, enhancing cell growth and survival, while the ETV6-NTRK3 fusion protein forms a complex with IGF1R, further driving its activation.