Chaperone-mediated Autophagy Governs Progression of Papillary Thyroid Carcinoma via PPARγ-SDF1/CXCR4 Signaling.
J Clin Endocrinol Metab
; 105(10)2020 10 01.
Article
en En
| MEDLINE
| ID: mdl-32556197
ABSTRACT
CONTEXT Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. Chaperone-mediated autophagy (CMA), 1 type of autophagy, is thought to promote or suppress cancer development in different cancer types. However, the effect of CMA on PTC development and the underlying mechanisms remain unknown. OBJECTIVE:
To determine whether CMA plays implied critical roles in the development of PTC.DESIGN:
We investigated the association between CMA and PTC development in PTC tissues and normal thyroid tissues by detecting the key protein of CMA, lysosome-associated membrane protein type 2A (LAMP2A), using quantitative polymerase chain reaction (PCR) and immunohistochemistry, which were further validated in the TGCA dataset. The effect of CMA on PTC development was studied by cell proliferation, migration, and apoptosis assays. The underlying mechanisms of peroxisome proliferator-activated receptor γ (PPARγ)-stromal cell-derived factor 1 (SDF1)/ C-X-C motif chemokine receptor 4 (CXCR4) signaling were clarified by western blotting, quantitative PCR, and rescue experiments. Knockdown and tamoxifen were used to analyze the effect of estrogen receptor (ER) α on CMA.RESULTS:
Our study confirmed that CMA, indicated by LAMP2A expression, was significantly increased in PTC tumor tissues and cell lines, and was associated with tumor size and lymph node metastasis of patients. Higher CMA in PTC promoted tumor cell proliferation and migration, thereby promoting tumor growth and metastasis. These effects of CMA on PTC were exerted by decreasing PPARγ protein expression to enhance SDF1 and CXCR4 expression. Furthermore, CMA was found positively regulated by ERα signaling in PTC.CONCLUSION:
Our investigation identified CMA regulated by ERα promoting PTC tumor progression that enhanced tumor cell proliferation and migration by targeting PPARγ-SDF1/CXCR4 signaling, representing a potential target for treatment of PTC.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Tiroides
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Antineoplásicos Hormonales
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Receptor alfa de Estrógeno
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Carcinogénesis
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Cáncer Papilar Tiroideo
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Autofagia Mediada por Chaperones
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Clin Endocrinol Metab
Año:
2020
Tipo del documento:
Article
País de afiliación:
China