Cdc42-KO Mouse

Cdc42, a member of the Rho family of small GTPases, is a master regulator of the actin cytoskeleton. It controls crucial cellular processes such as cell motility, polarity, and cell cycle progression. Cdc42 signals downstream of the master regulator Ras and is involved in the Ras-related signaling pathway [2,4,5]. It has been implicated in a wide range of biological functions, including cellular transformation, cell division, invasion, migration, and the formation of invadopodia, filopodia, as well as in maintaining cell polarity [1]. Studies in budding yeast (Saccharomyces cerevisiae) have provided insights into the regulation of Cdc42 for polarized growth, suggesting it has a conserved role in cell polarity establishment across different organisms [3].

Overexpression of Cdc42 is observed in several cancers, where it is linked to poor prognosis and tumour metastasis. In Ras-related cancers, enhanced Cdc42-signaling facilitates Ras-mediated cellular transformation, tumorigenesis, and metastasis. Some Cdc42 inhibitors have shown anticancer effects in Ras-related cancer cell lines derived from breast, colon, lung, and pancreatic cancer [4,5]. Additionally, Cdc42 is involved in the control of gametogenesis in the female reproductive system, playing a key role in the establishment of polarity in oocytes [6]. Aberrant expression of Cdc42, though mutations are rare, has been reported in various tumor types [7].

In conclusion, Cdc42 is essential for multiple biological functions including cell polarity, motility, and cell cycle regulation. Model-based research, such as studies in budding yeast, has provided valuable insights into its function. In the context of diseases, Cdc42's role in cancer, especially Ras-related cancers, and in gametogenesis in the female reproductive system, has been well-documented. Understanding Cdc42's function through these models may offer potential therapeutic strategies for related diseases.

References:

1. Qadir, Muhammad Imran, Parveen, Amna, Ali, Muhammad. 2015. Cdc42: Role in Cancer Management. In Chemical biology & drug design, 86, 432-9. doi:10.1111/cbdd.12556. https://pubmed.ncbi.nlm.nih.gov/25777055/

2. Murphy, Natasha P, Binti Ahmad Mokhtar, Ana Masara, Mott, Helen R, Owen, Darerca. . Molecular subversion of Cdc42 signalling in cancer. In Biochemical Society transactions, 49, 1425-1442. doi:10.1042/BST20200557. https://pubmed.ncbi.nlm.nih.gov/34196668/

3. Miller, Kristi E, Kang, Pil Jung, Park, Hay-Oak. 2020. Regulation of Cdc42 for polarized growth in budding yeast. In Microbial cell (Graz, Austria), 7, 175-189. doi:10.15698/mic2020.07.722. https://pubmed.ncbi.nlm.nih.gov/32656257/

4. Murphy, Natasha P, Mott, Helen R, Owen, Darerca. . Progress in the therapeutic inhibition of Cdc42 signalling. In Biochemical Society transactions, 49, 1443-1456. doi:10.1042/BST20210112. https://pubmed.ncbi.nlm.nih.gov/34100887/

5. Aguilar, Byron J, Zhou, Huchen, Lu, Qun. . Cdc42 Signaling Pathway Inhibition as a Therapeutic Target in Ras- Related Cancers. In Current medicinal chemistry, 24, 3485-3507. doi:10.2174/0929867324666170602082956. https://pubmed.ncbi.nlm.nih.gov/28571533/

6. Mei, Qiaojuan, Li, Huiying, Liu, Yu, Wang, Xiaofei, Xiang, Wenpei. 2021. Advances in the study of CDC42 in the female reproductive system. In Journal of cellular and molecular medicine, 26, 16-24. doi:10.1111/jcmm.17088. https://pubmed.ncbi.nlm.nih.gov/34859585/

7. Arias-Romero, Luis E, Chernoff, Jonathan. 2013. Targeting Cdc42 in cancer. In Expert opinion on therapeutic targets, 17, 1263-73. doi:10.1517/14728222.2013.828037. https://pubmed.ncbi.nlm.nih.gov/23957315/