Related Experiment Video
Updated: Feb 15, 2026
13:05
De Novo Generation of Somatic Stem Cells by YAP/TAZ
Published on: May 7, 2018
9.7K
Claudin-18-mediated YAP activity regulates lung stem and progenitor cell homeostasis and tumorigenesis
Beiyun Zhou1,2,3,4, Per Flodby1,2,3, Jiao Luo1,2,3
1Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine.
The Journal of Clinical Investigation
|February 6, 2018
Summary
Claudin 18 (CLDN18) loss in mice causes lung enlargement and promotes lung cancer by activating YAP. CLDN18 restricts organ size and progenitor proliferation, suggesting TJ disruption may enhance repair.
Area of Science:
- Cell Biology
- Cancer Biology
- Developmental Biology
Background:
- Claudins (TJ proteins) regulate permeability and polarity, with dysregulation common in cancer.
- The specific role of Claudin 18 (CLDN18) in cancer progression remains unclear.
- Lung alveolar epithelium highly expresses CLDN18.
Purpose of the Study:
- To investigate the role of CLDN18 in lung homeostasis and tumorigenesis.
- To elucidate the relationship between CLDN18, Yes-associated protein (YAP), and lung progenitor cell proliferation.
- To determine the impact of CLDN18 on organ size and cancer development.
Main Methods:
- Gene knockout (Cldn18-/-) and overexpression in mouse models.
- Analysis of lung morphology, progenitor cell abundance, and proliferation.
- Assessment of YAP activation and its downstream effects.
- Co-immunoprecipitation to study protein interactions (CLDN18 and YAP).
- Analysis of human lung adenocarcinoma (LuAd) for CLDN18 expression.
Main Results:
- Cldn18 knockout led to lung enlargement, increased alveolar epithelial type II (AT2) cell proliferation, and YAP activation.
- YAP inhibition reduced AT2 cell proliferation and prevented lung enlargement in Cldn18-/- mice.
- CLDN18 overexpression suppressed YAP activity, proliferation, and colony-forming efficiency.
- CLDN18 and YAP interact at cell-cell contacts; CLDN18 loss disrupts YAP interaction with Hippo kinases.
- Cldn18-/- mice showed increased lung adenocarcinoma incidence, and human LuAd exhibited reduced CLDN18.1 with stage progression.
Conclusions:
- CLDN18 acts as a critical regulator of YAP activity, restricting organ size and progenitor cell proliferation.
- Loss of CLDN18 promotes lung tumorigenesis by enhancing YAP signaling.
- Tight junction disruption may facilitate progenitor proliferation for tissue repair.
Related Concept Videos
01:02Glucose Homeostasis: Regulation of Blood Glucose
4.5K
Carbohydrates consumed through foods are converted into glucose, a crucial energy source for the body. In the prandial state, high blood glucose levels stimulate the secretion of insulin from the pancreas. Insulin inhibits hepatic glucose production and stimulates glucose uptake and metabolism by muscle and adipose tissue. The excess glucose is converted into glycogen and stored in the liver and muscles.
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
4.5K
01:01Regulation of Hematopoietic Stem Cells
4.1K
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
4.1K
01:16What is Homeostasis?
57.5K
Maintaining homeostasis requires that the body continuously maintain its internal conditions. Each physiological condition has a particular set point, from body temperature to blood pressure to levels of certain nutrients. A set point is the physiological value around which the normal range fluctuates. A normal range is a restricted set of values that is optimally healthful and stable. For example, the set point for normal human body temperature is approximately 37°C (98.6°F).
57.5K
01:31pH Homeostasis
20.1K
Acid-base homeostasis is essential for maintaining normal physiological activities in humans. The pH of various body fluids is strictly regulated because it is critical for the optimal activity of enzymes involved in metabolic reactions. Enzymes are basically proteins, so, any significant change in pH can affect their structure and activity. In humans, pH is regulated using three primary mechanisms— chemical buffer systems, respiratory regulation, and renal regulation.
Respiratory...
Respiratory...
20.1K
02:58Regulated Protein Degradation
8.9K
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.9K
01:28pH Regulation in Cells
7.8K
pH plays a critical role in maintaining normal cellular activities. It helps maintain the structure and function of various proteins, dictates the charge on cellular membranes, and is crucial for metabolic reactions inside the cell. Moreover, cells use the energy from the proton motive force to generate ATP.
Cytosolic pH
Under physiological conditions, the cytosolic pH is slightly more acidic than the extracellular pH. However, cells must prevent further acidification of their cytosol to...
Cytosolic pH
Under physiological conditions, the cytosolic pH is slightly more acidic than the extracellular pH. However, cells must prevent further acidification of their cytosol to...
7.8K