J Cancer 2021; 12(3):818-826. doi:10.7150/jca.45052

Research Paper

ADP-Ribosylation Factor Like GTPase 4C (ARL4C) augments stem-like traits of glioblastoma cells by upregulating ALDH1A3

Qian Chen1,3*, Wen-juan Fu1*, Xiao-peng Tang2, Lu Wang1, Qin Niu1, Shuai Wang1, Yong Lin1, Mian-fu Cao1, Rong Hu4, Hai-Yan Wen5, Yan Wang1, Xia Zhang1, Xiao-Hong Yao1✉

1. Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China.
2. Department of Nephrology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
3. Cancer Center of Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
4. Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
5. Department of Pathology, the Affiliated Provincial Hospital, Anhui Medical University, Hefei, China.
*These authors contributed equally to this work.

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Citation:
Chen Q, Fu Wj, Tang Xp, Wang L, Niu Q, Wang S, Lin Y, Cao Mf, Hu R, Wen HY, Wang Y, Zhang X, Yao XH. ADP-Ribosylation Factor Like GTPase 4C (ARL4C) augments stem-like traits of glioblastoma cells by upregulating ALDH1A3. J Cancer 2021; 12(3):818-826. doi:10.7150/jca.45052. Available from https://www.jcancer.org/v12p0818.htm

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Abstract

Glioma cells with stem cell-like properties are crucial for tumor initiation, progression and therapeutic resistance. Therefore, identifying specific factors in regulating stem-like traits is critical for the design of novel glioma therapeutics.

Herein, we reported that ADP-Ribosylation Factor Like GTPase 4C (ARL4C) was highly expressed in glioma stem-like cells (GSLCs). GSLCs, determined by the efficiency of sphere formation in vitro and tumor growth in vivo, was increased by overexpression of ARL4C. ARL4C induced the tumorigenesis through ALDH1A3. Analyses of 325 patient specimens showed that ARL4C was highly expressed in glioblastoma (GBM) as compared with lower grade gliomas. In addition, higher level ARL4C expression in glioma was correlated with poorer progression-free survival and overall survival of patients. Therefore, ARL4C may act as a novel prognostic marker and a therapeutic target for GBM.

Keywords: ARL4C, glioblastoma, glioma stem-like cell, ALDH1A3