Abstract
Ras association domain family 1A (RASSF1A) is one of the most epigenetically silenced elements in human cancers. Localized on chromosome 3, it has been demonstrated to be a bone fide tumor suppressor influencing cell cycle events, microtubule stability, apoptosis, and autophagy. Although it is epigenetically silenced by promoter-specific methylation in cancers, several somatic nucleotide changes (polymorphisms) have been identified in RASSF1A in tissues from cancer patients. We speculate that both nucleotide changes and epigenetic silencing result in loss of the RASSF1A tumor suppressor function and the appearance of enhanced growth. This paper will summarize what is known about the origin of these polymorphisms and how they have helped us understand the biological role of RASSF1A.
Highlights
Cancer is a disease affecting 1 in 3 adults worldwide and is considered to be the second leading cause of death in both Canada and the United States behind heart disease [1, 2]
We have shown that Ras association domain family 1A (RASSF1A) does not influence the intrinsic pathway of cell death [58]
We demonstrated that microtubule localization was required for association with death receptors and for the role of RASSF1A in apoptosis [13, 20]
Summary
Cancer is a disease affecting 1 in 3 adults worldwide and is considered to be the second leading cause of death in both Canada and the United States behind heart disease [1, 2]. In 2000, Hanahan and Weinberg systematically described several key features or “hallmarks” of cancer that defined the behavior of a cancer cell [6] These defining features of a cancer cell included the unique properties of limitless replicative potential, evasion of apoptosis, ability to stimulate neo-vascularization, invasion and metastasis, inhibition of suppressor pathways, and sustained proliferation. As described in their seminal paper, the aforementioned hallmarks are acquired through a “multistep process” that allows the cancer cells to acquire key survival traits while avoiding the watchful eye of established molecular “checkpoints” to inhibit abnormal growth [7]. Molecular Biology International have revealed interesting and surprising influences on numerous aspects of biology
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