T Cell CD Antigen

Overview of Claudins

Claudins are an important class of membrane proteins that serve as key components of intermediate tight junctions. Intermediate tight junctions are points of cell-to-cell connection located on the cell surface, playing a crucial role in maintaining cellular architecture stability and regulating the exchange of substances between the inside and outside of cells. Members of the claudin protein family share sequence similarities but have diverse functions. These proteins are primarily found in the epithelial cells at the cell-to-cell junctions, including tissues such as the intestine, renal tubules, and the blood-brain barrier. Claudins form a continuous physical barrier by interacting with corresponding proteins in adjacent cells, limiting the passage of fluids and solutes through the intercellular spaces.

As research on claudins advances, we have gained a clearer understanding of their functions and regulatory mechanisms. Studies have revealed that claudins not only regulate the selective transport of substances and ions between cells but also participate in maintaining cellular architecture, regulating signal transduction, and processes such as tumor invasion and metastasis. Scientists employ various techniques such as molecular biology, cell biology, biochemistry, immunology, and others to study claudins. Investigating claudins is of significant importance in elucidating the molecular mechanisms of cell-to-cell connections, understanding the formation and functionality of tissue barriers, and unraveling the mechanisms underlying related diseases. Further research may contribute to revealing the potential roles of claudins in disease diagnosis and treatment, as well as the development of related drugs and therapeutic approaches.

Table 1. Roles of claudins in human cancer. (Kwon M J, 2013)

Claudins	Cancer	Function	In vitro or in vivo	Role
Claudin-1	Breast	Increase of cell migration	In vitro	Cancer promoting
	Breast	Anti-apoptotic effect	In vitro	Cancer promoting
	Colon	Increase of invasion and metastatic behavior	In vitro & in vivo	Cancer promoting
	Liver	Increase of invasion	In vitro	Cancer promoting
	Liver	Induction of EMT	In vitro	Cancer promoting
	Melanoma	Increase of cell motility and invasion	In vitro	Cancer promoting
	Oral	Increase of invasion	In vitro	Cancer promoting
	Gastric	Inhibition of tumorigenicity	In vivo	Tumor suppressive
	Lung	Inhibition of cell migration and invasion, in vivo metastasis	In vitro & in vivo	Tumor suppressive
Claudin-3	Ovarian	Increase of invasion	In vitro	Cancer promoting
	Ovarian	Promoting in vivo tumor growth and metastasis	In vivo	Cancer promoting
	Ovarian	Inhibition of in vivo tumor growth and metastasis	In vitro & in vivo	Tumor suppressive
	Ovarian	Suppression of EMT	In vitro & in vivo	Tumor suppressive
Claudin-4	Ovarian	Increase of invasion	In vitro	Cancer promoting
	Ovarian	Stimulation of angiogenesis	In vitro & in vivo	Cancer promoting
	Gastric	Inhibition of migration and invasion	In vitro	Tumor suppressive
	Ovarian	Suppression of EMT	In vitro & in vivo	Tumor suppressive
	Pancreatic	Suppression of cell invasion and metastasis	In vitro & in vivo	Tumor suppressive
Claudin-6	Gastric	Increase of proliferation, migration and invasion	In vitro	Cancer promoting
	Breast	Inhibition of anchorage-independent growth	In vitro	Tumor suppressive
	Breast	Inhibition of anchorage-independent growth, migration and invasion	In vitro	Tumor suppressive
Claudin-7	Colorectal	Increase of cell proliferation and tumorigenicity	In vitro & in vivo	Cancer promoting
	Ovarian	Increase of invasion	In vitro	Cancer promoting
	Esophageal	Decrease of cell growth and invasion	In vitro	Tumor suppressive
	Lung	Inhibition of migration and invasion, in vivo tumor growth	In vitro & in vivo	Tumor suppressive
Claudin-11	Bladder	Inhibition of cell invasion	In vitro	Tumor suppressive
	Gastric	Inhibition of cell invasion	In vitro	Tumor suppressive

Research Areas of Claudins

• Cell Junctions and the epithelial barrier

Claudins regulate tight junctions between epithelial cells by interacting with other cell adhesion proteins to form intercellular junction complexes. Researchers have also focused on the effects of claudins on cell polarity and epithelial barrier function, as well as their regulatory mechanisms during epithelial tissue development and regeneration.

• Regulation of intercellular permeability

Claudins regulate intercellular permeability, controlling the passage of small molecules, ions, and solutes through epithelial and endothelial tissues. Researchers also explore differences in the expression and function of claudins in different tissues and organs, as well as their changes in disease progression (e.g., inflammatory bowel disease, kidney disease, and tumors). By studying the function of claudins, new clues can be provided to the pathogenesis of diseases and therapeutic strategies.

• Role in the nervous system

Claudins regulate connections between nerve cells, maintain the integrity of the blood-brain barrier, and are involved in neurological injury and inflammation-related diseases. Studies on the function of claudins in the nervous system can improve our understanding of neurodegenerative diseases and brain injury, and provide potential targets for the treatment of related diseases.

• Tumor biology

Recent studies have shown that claudins have a key role in cancer (as shown in table 1). They are involved in regulating the proliferation, migration, and invasion of tumor cells and influence the malignancy and prognosis of tumors. Researchers are committed to investigating the expression and regulatory mechanisms of claudins in different tumor types and their feasibility as potential therapeutic targets.

Overall, claudins have been studied in a variety of areas including cellular connectivity, intercellular permeability, epithelial barrier, nervous system, and tumor biology. With the continuous and in-depth study of claudins' functions and regulatory mechanisms, we are expected to further understand the important roles of claudins in biological processes as well as their mechanisms of action in diseases, which provides opportunities for the development of new therapeutic approaches and drugs.

Reference:

1. Kwon M J. Emerging roles of claudins in human cancer[J].International journal of molecular sciences, 2013, 14(9): 18148-18180.