Progranulin depletion inhibits proliferation via the transforming growth factor beta/SMAD family member 2 signaling axis in Kasumi-1 cells
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Author
Yabe, KuniakiYamamoto, Yasuko
Takemura, Masao
Hara, Takeshi
Tsurumi, Hisashi
Serrero, Ginette
Nabeshima, Toshitaka
Saito, Kuniaki
Date
2021-01-01Journal
HeliyonPublisher
Elsevier Ltd.Type
Article
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Show full item recordAbstract
Progranulin is an autocrine growth factor that promotes proliferation, migration, invasion, and chemoresistance of various cancer cells. These mechanisms mainly depend on the protein kinase B (Akt)/mechanistic target of rapamycin (mTOR) pathway. Recent studies have shown that patients with hematopoietic cancer have elevated serum progranulin levels. Thus, the current study aimed to investigate the role of progranulin in hematopoietic cancer cells and how it modulates their proliferation. Both knockdown of progranulin and progranulin neutralizing antibody treatment inhibited proliferation in several human hematopoietic cancer cell lines. Moreover, progranulin depletion not only decreases the phosphorylation level of the Akt/mTOR pathway but also, surprisingly, increases the expression of transforming growth factor-beta (TGF-β) and phosphorylation of mothers against decapentaplegic homolog 2 (SMAD2) in Kasumi-1 cell. Furthermore, LY2109761, an inhibitor of TGF-β receptor type I/II kinase, and TGF-β neutralizing antibody blocked the inhibition of proliferation induced by progranulin depletion. These data provide new insights that progranulin alters cell proliferation via the TGF-β axis and progranulin could be a new therapeutic target for hematopoietic cancers. © 2020 The Author(s)Sponsors
Smoking Research FoundationKeyword
Hematologic neoplasmsMechanistic target of rapamycin complex 1
Progranulin
Transforming growth factor beta
Identifier to cite or link to this item
http://hdl.handle.net/10713/14373ae974a485f413a2113503eed53cd6c53
10.1016/j.heliyon.2020.e05849