Illustration of a cell with a glowing primary cilium transmitting signals, symbolizing LKB1's role in cellular communication and disease prevention.

Unlocking the Secrets of Cellular Communication: How Primary Cilia Impact Disease and Health

Author's portrait.
Soraya Malik in Science & Nature June 2025 • 5 min read.

"A groundbreaking study reveals the critical role of LKB1 function in primary cilia, offering new insights into cancer and genetic disorders."


In the intricate world of cellular biology, the primary cilium stands out as a vital communication hub. This tiny, antenna-like structure projects from the surface of nearly every cell in the human body, playing a crucial role in sensing the environment and relaying signals that govern cell behavior. Its importance extends far beyond basic cell function, influencing development, tissue maintenance, and the onset of various diseases.

Recent research has illuminated the critical role of a protein known as LKB1 within the primary cilium. LKB1, a serine threonine kinase, is highly conserved throughout evolution, indicating its fundamental importance. It's ubiquitously expressed in human cells, where it acts as a master regulator of cellular energy and growth. However, its function within the primary cilium has remained relatively obscure until now.

This article delves into a groundbreaking study that uncovers a novel function of LKB1 in the primary cilium, shedding light on its potential implications for diseases like cancer and Peutz-Jeghers syndrome (PJS). By understanding how LKB1 operates within this cellular antenna, we can unlock new avenues for therapeutic intervention and improve human health.

LKB1: A Guardian Within the Cellular Antenna

Illustration of a cell with a glowing primary cilium transmitting signals, symbolizing LKB1's role in cellular communication and disease prevention.

LKB1 has long been recognized for its role as a tumor suppressor. Mutations in the LKB1 gene are causally linked to Peutz-Jeghers syndrome (PJS), an autosomal dominant inherited disorder characterized by the development of melanocytic macules (dark spots) on the lips and mouth, as well as the formation of multiple gastrointestinal hamartomatous polyps. PJS patients face a significantly increased risk of developing various malignant tumors, including those of the breast and gastrointestinal tract.

Further research has revealed that LKB1 expression is frequently lost in several types of cancer, including cervical, pancreatic, and lung carcinomas. This loss of LKB1 function contributes to uncontrolled cell growth and tumor formation. While the role of LKB1 as a tumor suppressor is well-established, the precise mechanisms by which it exerts this protective effect have remained a topic of ongoing investigation.

The study highlights several key findings:
  • LKB1 is constitutively active in cells: The LKB1 complex is constantly working, suggesting its regulation depends on where it is, not necessarily if it's on or off.
  • Intracellular Localization Matters: LKB1's location within the cell dictates its function, allowing it to interact with specific substrates at specific times.
  • Cilia are Key: While LKB1 can be found in the nucleus under certain conditions, it primarily resides in the cytosol, adherent junctions, and, importantly, the primary cilium in polarized epithelial cells.
  • Cilia Function Still Poorly Understood: How LKB1 functions in cilia is still not clear, even though its involvement in mTOR regulation has been proposed.
The researchers used a novel knockout mouse model to investigate the specific role of LKB1 in cilia. By selectively deleting LKB1 in these structures, they were able to pinpoint its unique contribution to cellular function. This approach allowed them to define a new LKB1 function within the cilium, one that may be critical for its tumor suppressor properties. These findings suggest that the primary cilium and LKB1 interplay is significant for cancer prevention.

Implications for Future Research and Therapies

The discovery of a new LKB1 function in the primary cilium opens up exciting possibilities for future research and therapeutic development. By further elucidating the molecular mechanisms by which LKB1 operates within this structure, scientists can gain a deeper understanding of its role in cancer and other diseases. This knowledge could lead to the development of targeted therapies that specifically modulate LKB1 activity in the cilium, potentially preventing or treating these conditions.

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.

Everything You Need To Know

1

What is a primary cilium and why is it important?

The primary cilium is a small, antenna-like structure found on the surface of nearly every cell in the human body. It acts as a communication hub, sensing the environment and relaying signals that control cell behavior. Its significance lies in its influence on development, tissue maintenance, and the development of various diseases, including cancer. Understanding its function is crucial for deciphering cellular communication.

2

What is LKB1, and why is it significant in relation to cancer and cellular function?

LKB1 is a protein, specifically a serine threonine kinase, that plays a vital role in cellular energy regulation and growth. It functions as a tumor suppressor, and mutations in the LKB1 gene are linked to Peutz-Jeghers syndrome (PJS) and increased cancer risk. LKB1's importance comes from its involvement in preventing uncontrolled cell growth and tumor formation. Understanding how LKB1 works in the cell can lead to finding potential treatments.

3

What is Peutz-Jeghers syndrome (PJS), and how is it related to LKB1?

Peutz-Jeghers syndrome (PJS) is an inherited disorder caused by mutations in the LKB1 gene. It is characterized by dark spots on the lips and mouth, and the formation of polyps in the gastrointestinal tract. PJS is significant because it increases the risk of developing various cancers. The connection between LKB1 and PJS highlights the gene's role in preventing tumor development.

4

What does it mean that LKB1 is constitutively active?

LKB1 is constitutively active in cells meaning that it's always 'on'. This suggests that its regulation depends more on its location within the cell, rather than being switched on or off. Its location dictates its function and allows it to interact with specific substrates at specific times. Knowing that LKB1 is always active changes how we view its regulatory function. This has significance for how therapies are developed.

5

How did the researchers study LKB1 in cilia, and why was this approach important?

The study used a novel knockout mouse model where LKB1 was selectively deleted in cilia. This enabled researchers to pinpoint the unique role of LKB1 in cellular function, specifically in the primary cilium. This approach is important because it allowed the researchers to define a new function of LKB1 within the cilium, shedding light on its tumor suppressor properties. Using this approach confirmed that primary cilium and LKB1 interplay is significant for cancer prevention.

Newsletter Subscribe

Subscribe to get the latest articles and insights directly in your inbox.