Among the world’s deadliest cancer oral cancer is ranked among the 6th and the most common cancer, there are about 7,00,000 cases reported every year around the world(22,23). For many years it was believed that Rho proteins were not mutated in pathological conditions. However, the advent of large-scale gene sequencing has revealed both gain-of-function and loss-of-function mutations in several Rho GTPases. These findings have implications for how these proteins might be targeted by therapeutic agents, and suggest potential adverse effects that such treatments might evoke (24,25). Mutation in the Rho family GTPases can cause melanoma, head and neck carcinoma, breast cancer, etc (26).
Eighty-five percent of oral cancer is caused by tobacco use. The amount of tobacco also accounts for the prognosis of cancer(27). Added to this second-hand smoke may increase a person’s chance of producing head and neck cancer. Alcohol consumption may also put up the risk factor of head and neck cancer(28). Using both tobacco and alcohol can, even more, increase the risk. Other risk factors include prolonged exposure of sun rays, Human Papilloma Virus, Epstein-Barr Virus, Gender men are two to three times more affected than female, people of age more than 40 years, poor oral and dental hygiene and environmental or occupational hazards Like paint fumes and chemical(29,30).
Studies utilized high-throughput next generation sequencing of the exons (exome sequencing) of 147(31) and 121(32) melanomas and healthy tissue-matched controls. Mutations appearing in multiple melanomas were identified, known as recurrent mutations. Among the many mutations identified, both studies found mutations in Rac1. Remarkably, the same Rac1 residue, proline 29 (P29), was substituted multiple times in both studies. While these mutations are likely drivers of melanoma, their low frequency might in part explain why they were not identified until the relatively recent availability of high-throughput exome sequencing techniques.
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The low frequency also suggests that melanoma formation is a variable process that can occur through multiple genetic pathways, only 5–10% of which involve Rac1(P29). This mutation is a well-characterized activating mutation, and is a frequently occurring Ras mutation in various cancer types (33) there is also emerging evidence that Rho proteins may be mutationally activated in other forms of cancer. For example, the RAC1(P29S) mutation has been reported in a head and neck tumor (34) as well as a breast tumor (35).
Recent work from laboratory further demonstrates the utility of using C. elegans developmental neurobiology as a platform to study oncogenesis, as we have shown that TIAM-1, a Rac GEF, acts downstream of CDC-42 and upstream of the Rac GTPases in a linear pathway that regulates neuronal development and protrusion downstream of the UNC-40/Deleted in colorectal cancer(DCC) receptor molecule(36). Further work in oncogene and tumor suppressor regulation and function in C. elegans, combined with data from other systems, will continue to reveal new insights into the pathological mechanisms underlying tumor formation, maintenance, and metastasis.
