Colorectal cancer and RASSF family—A special emphasis on RASSF1A

Abstract

The RAS‐association domain family, commonly referred to as RASSF, is a family of 10 members (RASSF1‐10) implicated in a variety of key biological processes, including cell cycle regulation, apoptosis and microtubule stability. Furthermore, RASSFs have been implicated in tumorigenesis and several family members are now thought to be tumor suppressors. As opposed to the KRAS oncogene, for which mutational activation is frequent in colorectal cancer (CRC), RASSFs are found to be silenced mainly by aberrant promoter methylation. In particular, RASSF1A, RASSF2 and RASSF5 methylation has been associated with CRC development, though the mechanisms of action remain poorly understood. This review focus on the current knowledge of RASSF inactivation in CRC, particularly RASSF1A, and on the implications RASSFs may have as potential biomarkers and for the development of new targeted therapies for CRC.

Gene promoter methylation in colorectal cancer and healthy adjacent mucosa specimens

“…35 Also in this case, RASSF1A methylation levels varied with studies ranging from 10-20% of CRC subjects up to 40-50%, with some authors observing RASSF1A methylation in early stages of CRC, and others reporting it more frequently methylated in later stages. [35][36][37] Some correlations with tumor stage were also observed in the present study.…”

β-catenin interaction with NHERF1 and RASSF1A methylation in metastatic colorectal cancer patients

“…Methylation-associated inactivation of RASSF1A, described in many colorectal samples [20], suggests a synergistic effect between the silencing of the tumor suppressor gene RASSF1A and activation of the oncogene KRAS. Thus, RASSF1A methylation represents an alternative mechanism of aberrant RAS signaling [21]. In colon cancer, the interaction between RAS and β-catenin activation was studied [22, 23].…”

Retracted: Promoter Methylation of theRASSF1AGene may Contribute to Colorectal Cancer Susceptibility: A Meta-Analysis of Cohort Studies

“…In recent years, the tumor-suppressor gene RASSF1A has been extensively investigated and a considerable amount of studies have identified that loss of expression of RASSF1A was shown to participate in the pathogenesis of a variety of human cancers, such as lung cancer and breast cancer, as well as CRC (Chen et al, 2012;Kang et al, 2012). Increasing evidence has shown that loss or aberrant expression of RASSF1A is thought to be significantly correlated with methylation of the CpG-island promoter sequence of RASSF1A, which may alter the function or activity of RASSF1A, thereby playing an important role in promoting the progression and metastasis of CRC (Kimura et al, 2009;Tommasi et al, 2011;Fernandes et al, 2013). Therefore, RASSF1A promoter methylation is generally postulated to be involved in the development and progression of CRC (Sinha et al, 2013).…”