Transglutaminase 2 Plays a Critical, but Context‐Specific Role in Glioblastoma Proliferation

Abstract

Glioblastoma multiforme (GBM) is the most aggressive and common form of adult primary brain tumors. GBMs are characterized by resistance to chemotherapy and radiation, and exhibit a high propensity for reoccurrence. Therefore, it is imperative to define molecular mechanisms that contribute to GBM tumor survival and proliferation. One possible protein that may contribute to GBM proliferation is the multifunctional protein transglutaminase 2 (TG2). TG2 has been shown to play a critical role in proliferation in other types of cancers, and therefore we investigated its role in GBMs. Given the heterogeneity of GBM tumors, we used various GBM cell lines as well as non‐serum containing GBM neurospheres to determine if the role of TG2 in GBMs was broadly applicable, or just relevant to certain populations. Additionally, the neurospheres used represent three different GBM subtypes: mesenchymal, proneural and classical. By the use of novel inhibitors and genetic manipulations of TG2, results show that in most, but not all, cell lines TG2 plays a critical role in the proliferative process of GBM cells. Given the heterogeneity of GBM tumors, it is not surprising that TG2 facilitates the proliferative process in only certain GBM subtypes. Nonetheless, as the understanding of signaling mechanisms that contribute to GBM proliferation increases, TG2 inhibitors may in the future be effective therapeutic agents for certain GBMs, as determined by specific genetic determinants.Support or Funding InformationNIH RO1 NS065825