Role of Glioma-associated GLI1 Oncogene in Carcinogenesis and Cancertargeted Therapy

Abstract

Glioma-associated oncogenes (GLIs) are zinc finger protein family members and downstream regulatory factors of the classic Hedgehog (Hh) signaling pathway. GLI proteins influence the growth and development of organisms and aid in tissue repair. However, aberrant expression of the GLI family member GLI1 promotes carcinogenesis by inducing epithelial-mesenchymal transition (EMT), angiogenesis, and other signaling pathways. Overexpression of GLI1 is thought to be an indicator of poor prognosis as well as a potential therapeutic target for cancers. GLI inhibitors such as zerumbone, GANT61, resveratrol, and cyclopamine depress the Hh pathway in vitro and in vivo cancer research, and other non-canonical pathways may also activate expression of GLI1. Here, we summarize GLI function in carcinogenesis and cancer-targeted therapy.

Deriving prognostic significance from a molecular subtype model of laryngeal carcinoma

“…Aberrant expression of GLI1 and its isoforms are involved in epigenetic modification, angiogenesis, hypoxia, cancer stem cells, human telomerase reverse transcriptase activity, DNA damage response, carcinogenesis, chemoresistance, and so on. 21,22 Further, GLI1 activation either through canonical or non-canonical signaling pathways has been confirmed in other cancers. GLI1 is therefore the most significant target for cancer therapy, 23 and GLI inhibitors such as zerumbone, GANT61, resveratrol, and cyclopamine depressed the HH pathway in prior in vitro and in vivo studies.…”

“…The primary function of GLI1 is in play during embryonic development. Aberrant expression of GLI1 and its isoforms are involved in epigenetic modification, angiogenesis, hypoxia, cancer stem cells, human telomerase reverse transcriptase activity, DNA damage response, carcinogenesis, chemoresistance, and so on 21,22 . Further, GLI1 activation either through canonical or non‐canonical signaling pathways has been confirmed in other cancers.…”

“…GLI1 is therefore the most significant target for cancer therapy, 23 and GLI inhibitors such as zerumbone, GANT61, resveratrol, and cyclopamine depressed the HH pathway in prior in vitro and in vivo studies. 22 Interestingly, GANT61 showed superior anti-cancer activity compared to other upstream targets of HH signaling. GLI1 inhibitors in combination with other chemotherapeutic agents a promising strategy for the treatment of many different malignancies.…”

“…Further, GLI1 activation either through canonical or non‐canonical signaling pathways has been confirmed in other cancers. GLI1 is therefore the most significant target for cancer therapy, 23 and GLI inhibitors such as zerumbone, GANT61, resveratrol, and cyclopamine depressed the HH pathway in prior in vitro and in vivo studies 22 . Interestingly, GANT61 showed superior anti‐cancer activity compared to other upstream targets of HH signaling.…”

Identification of Proteins and Genes Associated with Hedgehog Signaling Pathway Involved in Neoplasm Formation Using Text-Mining Approach

“…Despite the fact that a large set of studies has been performed, there are some open questions about the role of the Hh pathway in various types of tumors. Also, the particular mechanisms of Gli transcription factors are widely discussed, and additional details of Gli-associated regulation of the Hh pathway can shed light on the mechanisms of cancer progression [8] . The processes regulating non-canonical activation of the Hh pathway and their regulation in particular types of tumors are of interest.…”