Medical implications of cdc42 in Humans

 

 

 

 

 

 

 

 

 

 

 

 

 

cdc42 has been involved in many cancers and is currently a focal point in cancer research. Late studies suggest that cdc42 has a tissue specific role in tumorigenesis by either promoting or inhibiting tumour progression according to the cellular environment. It promotes cancer development through its function in the cell cycle mitotic division, cell polarity and cytokinesis, intracellular trafficking and regulation of transcription. cdc42 is regulated by  GTPases and various other regulatory proteins and is therefore prone to mutagenic control by the later which can be carcinogenic. Currently, cdc42 has not been associated with point mutations in its coding gene sequence; this supported by mounting evidence from collected breast cancer and colon samples.

 

 

Breast cancer:

 

In breast cancer, cdc42 levels are significantly elevated, compared to healthy tissues extracted from the same patient, suggesting a possible correlation between cdc42 upregulation and the development of breast cancer. Recent studies examined this potential link of cdc42 to breast cancer by employing murine models with breast carcinomas. The data obtained proposed that the dominant mutant expression of cdc42 in a group of mice reduced the number of focal contacts and inhibited colony formation in soft agar and cell growth  in vivo compared to the control group, indicative of a possible association. Moreover, overexpression of ErbB1 and ErbB2 in breast cancer patients has been linked to activation of cdc42 which drives the ErbB1’s cellular accumulation by regulating the c-Cbl function. Thus, cdc42 as well as the ErbB receptors have been proposed as targets for the development of novel therapeutic strategies and treatment modalities. 

 

 

Testicular cancer:

 

Western blot analyses have shown that cdc42 is overexpressed in testicular germ cell tumours compared to healthy counterparts. It has been found that cdc42 overexpression is considerably higher in tumours of higher stages than in those of lower stages. This is highly suggestive of cdc42’s involvement in testicular germ cell tumours.

 

 

Lymphomas and Bladder cancer:

 

Research outcomes in patients diagnosed with lymphomas or bladder cancer although limited, provided some initial evidence, suggesting that cdc42s' activation or expression is important in cancer development and progression. cdc42’s activation is augmented as a result of NPM-ALK, an oncogenic fusion protein, forming a complex with GEF VAV1 in Anaplastic large cell lymphoma (ALCL) cell line. This signalling event causes the cell shape and migration to be regulated. ALCL cells undergo apoptosis when cdc42 is genetically knocked-out or inhibited using secramine. This is also suggestive of cdc42’s key involvement in this type of cancer and highlights its potential as a therapeutic target.

 

 

Conclusion - Summary

 

cdc42 is implicated in many more types of cancer, namely head and neck squamous cell carcinomas, melanomas, colorectal cancers, hepatocellular carcinomas and lung cancer. Here we displayed three of the major ones where alterations in its functional capacity can have dentrimental effects in the physiology of humans. It can therefore be characterised as a protein of high significance and of primary research interest that could lead to the development of novel pharmacotherapies which could potentially substitude current palliative remedies that are impotent in tackling carcinogenic cells at the molecular level.

 

 

 

 

Reference:

 

1. Huret, Jean-Loup. 2015. CDC42 (cell division cycle 42 (GTP binding protein, 25kDa)). CDC42 (cell division cycle 42 (GTP binding protein, 25kDa)). Atlas of Genetics and Cytogenetics in Oncology and Haematology.

 

Available at: http://atlasgeneticsoncology.org/Genes/CDC42ID40012ch1p36.html. [Accessed 12 March 2015].