title: Chaperone-mediated autophagy regulates proliferation by targeting RND3 in gastric cancer.
abstract: LAMP2A is the key protein of chaperone-mediated autophagy (CMA), downregulation of LAMP2A leads to CMA blockade. CMA activation has been implicated in cancer growth, but the exact mechanisms are unclear. Elevated expression of LAMP2A was found in 8 kinds of tumors (n=747), suggesting that LAMP2A may have an important role in cancer progression. Unsurprisingly, LAMP2A knockdown in gastric cancer (GC) cells hindered proliferation, accompanied with altered expression of cell cycle-related proteins and accumulation of RND3/RhoE. Interactomic and KEGG analysis revealed that RND3 was a putative CMA substrate. Further study demonstrated that RND3 silencing could partly rescue the proliferation arrest induced by LAMP2A knockdown; RND3 was increased upon lysosome inhibition via both chemicals and LAMP2A-shRNA; Furthermore, RND3 could interact with CMA components HSPA8 and LAMP2A, and be engulfed by isolated lysosomes. Thus, constant degradation of RND3 by CMA is required to sustain rapid proliferation of GC cells. At last, the clinical significance of LAMP2A was explored in 593 gastric noncancerous lesions and 173 GC tissues, the results revealed that LAMP2A is a promising biomarker for GC early warning and prognosis of female GC patients.
authors.affiliation: a State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China.|b Department of Gastroenterology , The 264th hospital of PLA , Taiyuan , China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Zhou
authors.affiliation: a State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Yang
authors.affiliation: c Institute of Plastic Surgery of the Chinese PLA , Fourth Military Medical University , Xi'an , China.
authors.forename: Xing
authors.initials: X
authors.lastname: Fan
authors.affiliation: a State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China.
authors.forename: Sijun
authors.initials: S
authors.lastname: Hu
authors.affiliation: a State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China.
authors.forename: Fenli
authors.initials: F
authors.lastname: Zhou
authors.affiliation: a State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China.
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Dong
authors.affiliation: a State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China.
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.affiliation: a State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Shang
authors.affiliation: d Department of Biochemistry and Molecular Biology , Ningbo University School of Medicine , Zhejiang , China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Jiang
authors.affiliation: a State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China.
authors.forename: Hao
authors.initials: H
authors.lastname: Guo
authors.affiliation: a State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China.
authors.forename: Ning
authors.initials: N
authors.lastname: Chen
authors.affiliation: a State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xiao
authors.affiliation: e Department of Gastroenterology , General Hospital of Beijing Command , Beijing , China.
authors.forename: Jianqiu
authors.initials: J
authors.lastname: Sheng
authors.affiliation: a State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China.
authors.forename: Kaichun
authors.initials: K
authors.lastname: Wu
authors.affiliation: a State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China.
authors.forename: Yongzhan
authors.initials: Y
authors.lastname: Nie
authors.affiliation: a State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China.
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000912:Antibodies, Neoplasm / Q000378:metabolism; D001343:Autophagy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D052119:Lysosomal-Associated Membrane Protein 2 / Q000378:metabolism; D008297:Male; D008819:Mice, Nude; D018832:Molecular Chaperones / Q000378:metabolism*; D015999:Multivariate Analysis; D011379:Prognosis; D011485:Protein Binding; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D020741:rho GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000912:Antibodies, Neoplasm; D052119:Lysosomal-Associated Membrane Protein 2; D018832:Molecular Chaperones; C508705:RND3 protein, human; D020741:rho GTP-Binding Proteins
keywords: CMA; LAMP2A; RND3; gastric cancer; proliferation