致癌与突变杂志

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The Glycoprotein Growth Factor Progranulin Promotes Carcinogenesis and has Potential Value in Anti-cancer Therapy

Yonghua Zhang and Andrew Bateman

Progranulin (PGRN) is a secreted glycoprotein growth factor with tumorigenic roles in a variety of tumors including, among others, breast, ovarian, prostate, bladder, and liver cancer. In some patients, for example with breast, ovarian or liver cancers, high PGRN expression in tumors correlated with a worse outcome. Studies using cell lines and animal models provide evidence that PGRN promotes tumor cell proliferation, migration and survival, and induces drug resistance. Increasing or decreasing PGRN production enhances or inhibits respectively the growth of PGRN-sensitive tumors in vivo. PGRN activity is associated with p44/42 mitogen-activated protein kinase as well as phosphatidylinositol 3-kinases signaling pathways. In addition, PGRN may stimulate the formation of the tumor stroma. As an extracellular regulator of tumorgenesis, PGRN is a potential therapeutic target and biomarker of prognosis in the treatment of various cancers.