title: RACK1 promotes the proliferation of THP1 acute myeloid leukemia cells.
abstract: The receptor for activated C kinase 1 (RACK1), an adaptor protein implicated in the regulation of multiple signaling pathways, has been reported to contribute to the survival of leukemic progenitor cells by enhancing the activity of glycogen synthase kinase 3β (GSK3β). However, it remains unknown whether RACK1 also contributes to the oncogenic growth of acute myeloid leukemia (AML) cells. Here, we report that transient or stable silencing of endogenous RACK1 expression by RACK1 short hairpin RNAs (shRNAs) led to impaired proliferation of THP1 AML cells without inducing terminal differentiation. Further exploration revealed that RACK1 loss-of-function resulted in reduced GSK3β activity. GSK3β shRNA treatment showed similar effects to RACK1 loss-of-function. Our data collectively suggest that RACK1 contributes to THP1 cell proliferation through, at least partially, enhancing GSK3β activity. Thus, targeting RACK1 may have some important therapeutic implications in the treatment of AML.
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, Central South University, Changsha, 410078, People's Republic of China.
authors.forename: Dalin
authors.initials: D
authors.lastname: Zhang
authors.forename: Qingyang
authors.initials: Q
authors.lastname: Wang
authors.forename: Ting
authors.initials: T
authors.lastname: Zhu
authors.forename: Junxia
authors.initials: J
authors.lastname: Cao
authors.forename: Xueying
authors.initials: X
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Beifen
authors.initials: B
authors.lastname: Shen
authors.forename: Jiyan
authors.initials: J
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010587:Phagocytosis / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D020298:U937 Cells
chemical_list: D018950:Lipopolysaccharide Receptors; D009363:Neoplasm Proteins; C419368:RACK1 protein, human; D034741:RNA, Small Interfering; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D019204:GTP-Binding Proteins