Astrocyte Elevated Gene-1: Unraveling the Journey from Oncogene to Colon Cancer Stem Cell Therapeutic Target

Colon cancer originates from the gastrointestinal epithelium, which undergo subsequent mutations in specific DNA sequences that interrupt normal mechanisms of cell proliferation and self-renewal. Such mutations are caused due to genetic alterations, alcohol, smoking, environmental carcinogens and chronic inflammatory states, where these pathological changes lead to transformation of a healthy colonic mucosa into an invasive colon cancer. Owing to their long life and their capacity for self-renewal, stem cells residing in the gastrointestinal tract represent the natural target of tumorigenic mutations where it might take only a few mutations for a colon cell to lose control over its self-renewal and growth, thereby transforming into colon cancer stem cells (CCSCs). These CCSCs are a subset of cancer cells with distinctive properties of self-renewal, infinite division and differentiation potential. Recent studies have emphasized the involvement of CCSCs in metastasis, tumor relapse and chemoresistance. Astrocyte Elevated Gene-1 (AEG1), a well-known oncogene and a crucial mediator of metastasis, contributes widely to colon cancer tumor growth, drug resistance, relapse, and metastasis, but its molecular mechanisms of action are not well elucidated. Previous studies suggests that AEG-1 is upregulated in most types of cancers, including colon cancer, plays a significant role linking various signaling pathways in tumorigenesis. Currently, the validated therapies against colon cancer have various limitations that frequently lead to failure of treatments where resistance to chemotherapy and radiotherapy are the prime causes of treatment failures. As the current therapies fail to eliminate CCSCs leading to metastasis and tumor recurrence, therefore, eliminating CCSCs is crucial in order to treat malignant colon cancer. Recently, multiple targets are being identified and potential agents are being developed that could specifically target CCSCs. Thus, deepening the understanding of AEG-1 function in colon cancer helps us to unravel how AEG-1 acts as a novel therapeutic target in eliminating CCSCs.

Author(s): Sushmitha Sriramulu

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