Symbolic illustration of AKT-PKM2 phosphorylation driving cancer cell growth.

IGF-1's Secret Weapon: How PKM2 Phosphorylation Drives Cancer Cell Growth

Rhea Morgan in Health & Wellness August 2025 • 4 min read.

"Unlocking the AKT-PKM2 Connection for Novel Cancer Therapies."

Insulin-like Growth Factor 1 (IGF-1) is a key player in the microenvironment surrounding tumors. It acts like a signal booster, encouraging cancer cells to grow and survive. While IGF-1's role in cancer has been known, the precise mechanisms are still being unraveled.

New research sheds light on a critical piece of this puzzle: a protein called pyruvate kinase muscle type 2 (PKM2). PKM2 undergoes changes after it's created (post-translational modifications) in response to signals from its surroundings, and these changes can significantly impact cancer cell behavior. Scientists have discovered how PKM2 gets activated in response to IGF-1, making it a potential weak spot for future cancer therapies.

This article dives into how AKT, another important protein in cell signaling, directly interacts with PKM2. This interaction leads to PKM2 phosphorylation, a process that's essential for PKM2 to move into the nucleus of cancer cells and drive tumor growth. Understanding this process opens doors to novel strategies for combating cancers driven by IGF-1 signaling.

The AKT-PKM2 Connection: A New Target for Cancer?

Symbolic illustration of AKT-PKM2 phosphorylation driving cancer cell growth.

The study highlights a specific chain of events: AKT, a protein kinase, directly interacts with PKM2 and phosphorylates it at a specific location (Ser-202). This phosphorylation is a crucial step that allows PKM2 to move into the cell's nucleus when stimulated by IGF-1. Once inside the nucleus, PKM2 gets cozy with another protein called STAT5A. This partnership boosts the production of cyclin D1, a protein that encourages cell division and growth. It’s like PKM2 is acting as a key to unlock STAT5A's potential to accelerate cancer cell growth under IGF-1's influence.

Researchers conducted several experiments to confirm this AKT-PKM2 relationship:

Blocking PKM2: When PKM2 was suppressed, the cancer cells' ability to grow in response to IGF-1 was significantly reduced.
AKT Inhibition: Preventing AKT from activating blocked PKM2's movement to the nucleus.
STAT5A's Role: If cells lacked PKM2, simply adding more STAT5A couldn't restore the cancer cells' growth response to IGF-1. However, if PKM2 was reintroduced, the cells regained their ability to grow when exposed to IGF-1.

These experiments confirmed that PKM2 plays a vital role in IGF-1-driven cancer cell growth. The phosphorylation of PKM2 by AKT is the essential step that allows PKM2 to activate STAT5A and promote cell division. This discovery suggests that targeting PKM2 could be a promising strategy for treating cancers that rely on dysregulated IGF/PI3K/AKT signaling.

Implications and Future Directions

This research highlights the significance of PKM2 as a potential therapeutic target. By understanding how AKT activates PKM2, scientists can develop drugs that disrupt this interaction, potentially slowing down or stopping cancer cell growth.

While this study focused on lung cancer cells, the IGF-1/AKT/PKM2 pathway is relevant in various cancer types. This makes the findings broadly applicable and opens avenues for developing treatments that target multiple cancers.

Further research is needed to fully understand how PKM2 interacts with STAT5A and regulates gene expression. Unlocking these details could lead to even more precise and effective cancer therapies. The discovery that PKM2 phosphorylation at Ser-202 is crucial for its interaction with STAT5 offers a specific target for drug development.

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: 10.18632/oncotarget.10179, Alternate LINK

Title: Akt-Induced Pkm2 Phosphorylation Signals For Igf-1-Stimulated Cancer Cell Growth

Subject: Oncology

Journal: Oncotarget

Publisher: Impact Journals, LLC

Authors: Young Soo Park, Dong Joon Kim, Han Koo, Se Hwan Jang, Yeon-Mi You, Jung Hee Cho, Suk-Jin Yang, Eun Sil Yu, Yuri Jung, Dong Chul Lee, Jung-Ae Kim, Zee-Yong Park, Kyung Chan Park, Young Il Yeom

Published: 2016-06-20

Everything You Need To Know

What is Insulin-like Growth Factor 1 (IGF-1), and why is it important in this context?

Insulin-like Growth Factor 1 (IGF-1) is a molecule found in the microenvironment around tumors. Its primary function is to act as a signal booster, stimulating cancer cells to grow and survive. The significance lies in its ability to promote cancer cell proliferation, making it a crucial factor in tumor development and progression. Understanding IGF-1's role is fundamental in identifying potential therapeutic targets for cancer treatment.

What is PKM2, and why is it significant in this research?

PKM2 (pyruvate kinase muscle type 2) is a protein that undergoes post-translational modifications in response to signals from its surroundings. The importance of PKM2 is in its involvement in cancer cell growth when activated by IGF-1. Specifically, the phosphorylation of PKM2 allows it to move into the cell's nucleus, interact with STAT5A, and promote cell division. This suggests that targeting PKM2 could be a promising strategy for treating cancers.

What role does AKT play in the process, and why is it important?

AKT is a protein kinase that directly interacts with PKM2 and phosphorylates it. This phosphorylation is a crucial step, enabling PKM2 to move into the cell's nucleus. The implications of AKT's role are significant, as it connects IGF-1 signaling to PKM2 activation, thus driving tumor growth. Inhibiting AKT could block PKM2's movement to the nucleus, offering a strategy for disrupting the cancer cell's growth cycle. This opens avenues for novel cancer therapies.

What is PKM2 phosphorylation and why is it important in the context of cancer?

PKM2 phosphorylation is a post-translational modification of PKM2, a process where a phosphate group is added to the protein. This phosphorylation, specifically at Ser-202, is essential for PKM2 to move into the nucleus and interact with STAT5A. This interaction increases the production of cyclin D1. The importance lies in the direct link between this process and cancer cell proliferation under the influence of IGF-1. The implications are that blocking PKM2 phosphorylation could be a therapeutic strategy to slow or stop cancer cell growth.

What role does STAT5A play in cancer cell growth in this research?

STAT5A is a protein that interacts with PKM2 in the nucleus of cancer cells. The significance of this partnership is that it boosts the production of cyclin D1, promoting cell division and growth. Experiments showed that without PKM2, adding STAT5A alone couldn't restore cancer cell growth in response to IGF-1. However, when PKM2 was reintroduced, the cells regained their ability to grow when exposed to IGF-1. This confirms PKM2's crucial role in activating STAT5A and accelerating cancer cell growth under IGF-1's influence. Targeting STAT5A is another possible approach.