title: High expression of leptin receptor leads to temozolomide resistance with exhibiting stem/progenitor cell features in gliobalastoma.
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.
authors.affiliation: Department of Neurosurgery; Changhai Hospital; Second Military Medical University; Shanghai, China.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Han
authors.affiliation: Department of Neurosurgery; Changhai Hospital; Second Military Medical University; Shanghai, China.
authors.forename: Laixing
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery; Changhai Hospital; Second Military Medical University; Shanghai, China.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery; Changhai Hospital; Second Military Medical University; Shanghai, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Yue
authors.affiliation: Department of Neurosurgery; Changhai Hospital; Second Military Medical University; Shanghai, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery; Changhai Hospital; Second Military Medical University; Shanghai, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurosurgery; Changhai Hospital; Second Military Medical University; Shanghai, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery; Changhai Hospital; Second Military Medical University; Shanghai, China.
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery; Changhai Hospital; Second Military Medical University; Shanghai, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Liu
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor / Q000187:drug effects; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D054411:Receptors, Leptin / Q000235:genetics* / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D000077204:Temozolomide
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D018906:Antineoplastic Agents, Alkylating; D006023:Glycoproteins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D010455:Peptides; D054411:Receptors, Leptin; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D050796:STAT3 Transcription Factor; D003606:Dacarbazine; D000077204:Temozolomide
keywords: STAT3; chemoresistance; glioblastoma stem cells; leptin receptor