FAM72, Glioblastoma Multiforme (GBM) and Beyond

Abstract

Neural stem cells (NSCs) offer great potential for regenerative medicine due to their excellent ability to differentiate into various specialized cell types of the brain. In the central nervous system (CNS), NSC renewal and differentiation are under strict control by the regulation of the pivotal SLIT-ROBO Rho GTPase activating protein 2 (SRGAP2)—Family with sequence similarity to the 72 (FAM72) master gene (i.e., |-SRGAP2–FAM72-|) via a divergent gene transcription activation mechanism. If the gene transcription control unit (i.e., the intergenic region of the two sub-gene units, SRGAP2 and FAM72) gets out of control, NSCs may transform into cancer stem cells and generate brain tumor cells responsible for brain cancer such as glioblastoma multiforme (GBM). Here, we discuss the surveillance of this |-SRGAP2–FAM72-| master gene and its role in GBM, and also in light of FAM72 for diagnosing various types of cancers outside of the CNS.

Identification of a Chemotherapeutic Lead Molecule for the Potential Disruption of the FAM72A-UNG2 Interaction to Interfere with Genome Stability, Centromere Formation, and Genome Editing

“…Of note, withaferin A has been reported to be a potential anti-cancer molecule that can inhibit cell proliferation, cell migration, and cell invasion [ 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 ]. Similarly, withaferin B, bound to the FAM72A-UNG2 heterodimer, could possibly block FAM72A-UNG2 signaling pathways in cancer cells [ 26 , 29 ]; however, thus far, the biological and therapeutic properties of withaferin B remain unknown.…”

“…Accumulating evidence indicates the involvement of FAM72A in tumorigenesis [ 24 , 25 , 26 , 29 , 87 , 88 ]. Elevated FAM72A causes reduced UNG2 levels, eventually leading to new mutations [ 24 , 25 , 27 , 28 , 29 ].…”

“…Thus, FAM72A bridges BER and mismatch repair in order to modulate antibody diversification during B cell and antibody maturation [ 27 , 28 ]. Overall, an increased FAM72A level could lead to reduced UNG2 levels and could thus shift the balance of appropriate mutagenic DNA repair, therefore making the cells more susceptible to mutations, with possible effects on tumor development [ 24 , 25 , 27 , 28 , 29 ].…”

Novel Treatment Strategies for Glioblastoma—A Summary

“…Even though there have been limited advances in the progression of GBM therapeutics to significantly increase patient survival compared to other cancers, this has not dampened the motivation of researchers and clinicians to investigate novel treatment strategies for combating this disease. The Special Issue, ‘Novel Treatment Strategies for Glioblastoma’ [ 3 ], contains twelve articles (five original research articles and seven reviews) that explore a range of novel and strategic approaches for improving the treatment of GBM [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. This editorial aims to briefly summarize the content of these articles.…”

“…Ho et al [ 13 ] discuss the role of the gene pair |-SRGAP2–FAM72-| in the cell cycle and GBM, with the possibility of defining new therapeutic possibilities for GBM. Endogenous FAM72 expression has been detected in the hippocampal dentate gyrus, where the |-SRGAP2–FAM72-| master gene pair regulates neural stem cell (NSC) renewal, neurogenesis and brain plasticity.…”