Skip to Content
Merck

ATG4B promotes colorectal cancer growth independent of autophagic flux.

Autophagy (2014-07-06)
Pei-Feng Liu, Chung-Man Leung, Yu-Hsiang Chang, Jin-Shiung Cheng, Jih-Jung Chen, Chung-Jeu Weng, Kuo-Wang Tsai, Chien-Jen Hsu, Yen-Chen Liu, Ping-Chi Hsu, Hung-Wei Pan, Chih-Wen Shu
ABSTRACT

Autophagy is reported to suppress tumor proliferation, whereas deficiency of autophagy is associated with tumorigenesis. ATG4B is a deubiquitin-like protease that plays dual roles in the core machinery of autophagy; however, little is known about the role of ATG4B on autophagy and proliferation in tumor cells. In this study, we found that ATG4B knockdown induced autophagic flux and reduced CCND1 expression to inhibit G 1/S phase transition of cell cycle in colorectal cancer cell lines, indicating functional dominance of ATG4B on autophagy inhibition and tumor proliferation in cancer cells. Interestingly, based on the genetic and pharmacological ablation of autophagy, the growth arrest induced by silencing ATG4B was independent of autophagic flux. Moreover, dephosphorylation of MTOR was involved in reduced CCND1 expression and G 1/S phase transition in both cells and xenograft tumors with depletion of ATG4B. Furthermore, ATG4B expression was significantly increased in tumor cells of colorectal cancer patients compared with adjacent normal cells. The elevated expression of ATG4B was highly correlated with CCND1 expression, consistently supporting the notion that ATG4B might contribute to MTOR-CCND1 signaling for G 1/S phase transition in colorectal cancer cells. Thus, we report that ATG4B independently plays a role as a positive regulator on tumor proliferation and a negative regulator on autophagy in colorectal cancer cells. These results suggest that ATG4B is a potential biomarker and drug target for cancer therapy.

MATERIALS
Product Number
Brand
Product Description

Supelco
Sodium dodecyl sulfate, dust-free pellets, suitable for electrophoresis, for molecular biology, ≥99.0% (GC)
Supelco
Sodium dodecyl sulfate, suitable for ion pair chromatography, LiChropur, ≥99.0%
Sigma-Aldrich
Sodium dodecyl sulfate, ≥98.0% (GC)
Sigma-Aldrich
Sodium dodecyl sulfate solution, BioUltra, for molecular biology, 10% in H2O
Sigma-Aldrich
Ammonium chloride, for molecular biology, suitable for cell culture, ≥99.5%
Sigma-Aldrich
Propidium iodide, ≥94.0% (HPLC)
Sigma-Aldrich
Sodium dodecyl sulfate, BioXtra, ≥99.0% (GC)
Sigma-Aldrich
Sodium dodecyl sulfate, ReagentPlus®, ≥98.5% (GC)
Sigma-Aldrich
Sodium dodecyl sulfate, ≥98.0% (GC)
Sigma-Aldrich
Sodium dodecyl sulfate solution, BioUltra, for molecular biology, 20% in H2O
Sigma-Aldrich
Propidium iodide, ≥94% (HPLC)
Sigma-Aldrich
Sodium dodecyl sulfate, ACS reagent, ≥99.0%
Sigma-Aldrich
Sodium dodecyl sulfate, tested according to NF, mixture of sodium alkyl sulfates consisting mainly of sodium dodecyl sulfate
Sigma-Aldrich
Sodium dodecyl sulfate, BioReagent, suitable for electrophoresis, for molecular biology, ≥98.5% (GC)
Sodium laurilsulfate, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Sodium deoxycholate, ≥97% (titration)
Sigma-Aldrich
Propidium iodide solution
Sigma-Aldrich
Sodium dodecyl sulfate, ≥99.0% (GC), dust-free pellets
Sigma-Aldrich
Sodium dodecyl sulfate, ≥90% ((Assay))
Sigma-Aldrich
Sodium dodecyl sulfate, BioUltra, for molecular biology, ≥99.0% (GC)
Sigma-Aldrich
Sodium dodecyl sulfate, 92.5-100.5% based on total alkyl sulfate content basis
Sigma-Aldrich
Sodium dodecyl sulfate, BioReagent, suitable for electrophoresis, for molecular biology, ≥98.5% (GC), free-flowing, Redi-Dri
Sigma-Aldrich
tert-Butyl acetoacetate, reagent grade, 98%
Sigma-Aldrich
MISSION® esiRNA, targeting human ATG4B
SAFC
Sodium chloride solution, 5 M