Colorectal cancer cells respond differentially to autophagy inhibition in vivo

Scientific Reports
Annie LauzierSteve Jean

Abstract

Autophagy has both tumor-promoting and -suppressing effects in cancer, including colorectal cancer (CRC), with transformed cells often exhibiting high autophagic flux. In established tumors, autophagy inhibition can lead to opposite responses resulting in either tumor cell death or hyperproliferation. The functional mechanisms underlying these differences are poorly understood. The present study aimed to investigate the relationship between the autophagic capacities of CRC cells and their sensitivities to autophagy inhibition. All studied CRC cell lines showed high basal autophagic flux. However, only HCT116 and Caco-2/15 cells displayed regulated autophagic flux upon starvation. Knockdown of ATG5 (which disrupts autophagosome elongation) or RAB21 (which decreases autophagosome/lysosome fusion) had little effect on CRC cell proliferation in vitro. Nonetheless, inhibition of autophagy in vivo had a substantial cell line-dependent impact on tumor growth, with some cells displaying decreased (HCT116 and Caco-2/15) or increased (SW480 and LoVo) proliferation. RNA sequencing and Western blot analyses in hyperproliferative SW480 tumors revealed that the mTORC2 and AKT pathways were hyperactivated following autophagy impairment. Inhib...Continue Reading

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Jul 15, 2020·Nature Reviews. Urology·Livia Lacerda Mariano, Molly A Ingersoll
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Jul 25, 2021·Cancers·Mona Foth, Martin McMahon

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Methods Mentioned

BETA
lipidation
transmission electron microscopy
gene knockdown
Profiler
RNA-Seq
transfection
Assay
confocal microscopy

Software Mentioned

CellProfiler
Subread
Trimmomatic
FastQC
ImageJ
STAR
Illustrator
ImageLab
Ensembl
DESeq

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