High expression of leptin receptor leads to temozolomide resistance with exhibiting stem/progenitor cell features in gliobalastoma |
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Authors: | Guosheng Han Laixing Wang Wenyuan Zhao Zhijian Yue Rui Zhao Yanan Li Xiaoping Zhou Xiaowu Hu Jianmin Liu |
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Affiliation: | Department of Neurosurgery; Changhai Hospital; Second Military Medical University; Shanghai, China |
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Abstract: | Glioblastoma is a highly aggressive malignant disease with notable resistance to chemotherapy. In this study, we found that leptin receptor (ObR)-positive glioblastoma cells were resistant to temozolomide (TMZ), and TMZ-resistant cells exhibited high expression of ObR. ObR can serve as a marker to enrich glioblastoma cells with some stem/progenitor cell traits, which explained the reason for TMZ resistance of ObR+ cells. STAT3-mediated SOX2/OCT4 signaling axis maintained the stem/progenitor cell properties of ObR+ cells, which indirectly regulated glioblastoma TMZ resistance. These findings gain insight into the molecular link between obesity and glioblastoma, and better understanding of this drug-resistant population may lead to the development of more effective therapeutic interventions for glioblastoma. |
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Keywords: | chemoresistance STAT3 leptin receptor glioblastoma stem cells |
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