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Flotillin-1 palmitoylation turnover by APT-1 and ZDHHC-19 promotes cervical cancer progression by suppressing IGF-1 receptor desensitization and proteostasis
by
Jang, Donghwan
, Kwon, Hayeong
, Ahn, Yujin
, Pak, Yunbae
, Choi, Moonjeong
in
Cancer therapies
/ Cell activation
/ Cell growth
/ Cell proliferation
/ Cervical cancer
/ Endocytosis
/ Enzymes
/ Gene expression
/ Gene therapy
/ Human papillomavirus
/ Insulin
/ Insulin-like growth factor I
/ Insulin-like growth factors
/ Life sciences
/ Lysosomes
/ Mesenchyme
/ Metabolism
/ Palmitoylation
/ Palmitoyltransferase
/ Plasmids
/ Proteins
/ Reagents
/ Tiam1 protein
/ Wound healing
/ Zinc finger proteins
2023
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Flotillin-1 palmitoylation turnover by APT-1 and ZDHHC-19 promotes cervical cancer progression by suppressing IGF-1 receptor desensitization and proteostasis
by
Jang, Donghwan
, Kwon, Hayeong
, Ahn, Yujin
, Pak, Yunbae
, Choi, Moonjeong
in
Cancer therapies
/ Cell activation
/ Cell growth
/ Cell proliferation
/ Cervical cancer
/ Endocytosis
/ Enzymes
/ Gene expression
/ Gene therapy
/ Human papillomavirus
/ Insulin
/ Insulin-like growth factor I
/ Insulin-like growth factors
/ Life sciences
/ Lysosomes
/ Mesenchyme
/ Metabolism
/ Palmitoylation
/ Palmitoyltransferase
/ Plasmids
/ Proteins
/ Reagents
/ Tiam1 protein
/ Wound healing
/ Zinc finger proteins
2023
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Flotillin-1 palmitoylation turnover by APT-1 and ZDHHC-19 promotes cervical cancer progression by suppressing IGF-1 receptor desensitization and proteostasis
by
Jang, Donghwan
, Kwon, Hayeong
, Ahn, Yujin
, Pak, Yunbae
, Choi, Moonjeong
in
Cancer therapies
/ Cell activation
/ Cell growth
/ Cell proliferation
/ Cervical cancer
/ Endocytosis
/ Enzymes
/ Gene expression
/ Gene therapy
/ Human papillomavirus
/ Insulin
/ Insulin-like growth factor I
/ Insulin-like growth factors
/ Life sciences
/ Lysosomes
/ Mesenchyme
/ Metabolism
/ Palmitoylation
/ Palmitoyltransferase
/ Plasmids
/ Proteins
/ Reagents
/ Tiam1 protein
/ Wound healing
/ Zinc finger proteins
2023
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Flotillin-1 palmitoylation turnover by APT-1 and ZDHHC-19 promotes cervical cancer progression by suppressing IGF-1 receptor desensitization and proteostasis
Journal Article
Flotillin-1 palmitoylation turnover by APT-1 and ZDHHC-19 promotes cervical cancer progression by suppressing IGF-1 receptor desensitization and proteostasis
2023
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Overview
We have shown that insulin-like growth factor-1 (IGF-1) induces palmitoylation turnover of Flotillin-1 (Flot-1) in the plasma membrane (PM) for cell proliferation, after IGF-1 receptor (IGF-1R) signaling activation. However, the enzymes responsible for the turnover have not been identified. Herein, we show that acyl protein thioesterases-1 (APT-1) catalyzes Flot-1 depalmitoylation, and zinc finger DHHC domain-containing protein palmitoyltransferase-19 (ZDHHC-19) repalmitoylation of the depalmitoylated Flot-1 for the turnover in cervical cancer cells. The turnover prevented desensitization of IGF-1R via endocytosis and lysosomal degradation, thereby exerting excessive IGF-1R activation in cervical cancer cells. FLOT1, LYPLA1 and ZDHHC19 were highly expressed, and epithelial-to-mesenchymal transition (EMT)-inducing TIAM1 and GREM1 coordinately upregulated in malignant cervical cancer tissues. And blocking the turnover suppressed the EMT, migration, and invasion of cervical cancer cells. Our study identifies the specific enzymes regulating Flot-1 palmitoylation turnover, and reveals a novel regulatory mechanism of IGF-1-mediated cervical cancer progression.
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