In-silico analysis of Adenomatous Polyposis Coli (APC) gene in human cancers

Summary of the project:
Adenomatous Polyposis Coli is (APC) serves as a key tumor suppressor gene by suppressing canonical Wnt signaling pathway which is essential for tumorigenesis. It has several other cellular roles in conjunction with actin cytoskeleton and microtubule. To list few, cell-cell adhesion, migration, organization of mitotic spindle and chromosome segregation. Defects in any one of these processes leads to cancer progression, tumorigenesis and metastasis. Mutation in APC has been observed in more that 80% of colorectal cancers and more than 90% of these mutations result in the production of truncated proteins. Germline mutation in APC results in an inherited disorder called Familial Adenomatous Polyposis (FAP), characterized by the development of multiple benign polyps in the colon that eventually, with age, become malignant. The onset of FAP varies from age 35 to 55, depending on the speed of polyp growth. Individuals with FAP may have increased chance for developing cancer in other organs such as stomach, small intestine and pancreas. Depending on the association of FAP with extracolonic manifestation, FAP is further subdivided. Children with FAP may have high chances of hepatoblastoma. Since it is an inherited condition, mutation in APC can be used as a biomarker to predict the FAP in the family with a history of FAP. Although mutation in APC has been well characterized in colorectal cancers, several studies and databases have shown its varied expression levels in other cancers as well. Due to the clinical importance APC mutation or expression have been studied extensively. As discussed earlier, APC has diverse cellular functions that are required for the maintenance of cellular homeostasis to prevent tumorigenesis. Hence, a part of our interest is to report whether there is an association between a pathway that involves APC and cancer progression. One of the studied pathways that involves APC and tumorigenesis is Wnt signaling pathway, as we discussed in the beginning. Additionally, later part of our review study involves studying mutational and expression profiles of APC and their association with cancers.

Funding body: NA
Funding year: NA
Funding Year: 2018
Mentor: Roshan Lal Shrestha, PhD., Center for Health and Disease Studies Nepal (CHDS-Nepal)
Thesis student: Aroz Hada, Department of Biotechnology, Kathmandu University
Status: Complete
Publication: Not Yet