PMID- 32556197 OWN - NLM STAT- MEDLINE DCOM- 20210219 LR - 20210816 IS - 1945-7197 (Electronic) IS - 0021-972X (Linking) VI - 105 IP - 10 DP - 2020 Oct 1 TI - Chaperone-mediated Autophagy Governs Progression of Papillary Thyroid Carcinoma via PPARgamma-SDF1/CXCR4 Signaling. LID - dgaa366 [pii] LID - 10.1210/clinem/dgaa366 [doi] AB - 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 gamma (PPARgamma)-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) alpha 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 PPARgamma protein expression to enhance SDF1 and CXCR4 expression. Furthermore, CMA was found positively regulated by ERalpha signaling in PTC. CONCLUSION: Our investigation identified CMA regulated by ERalpha promoting PTC tumor progression that enhanced tumor cell proliferation and migration by targeting PPARgamma-SDF1/CXCR4 signaling, representing a potential target for treatment of PTC. CI - (c) Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Zhou, Hong AU - Zhou H AD - Department of Endocrinology and Metabolism, Center for Microbiota and Immunological Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Xie, Xin AU - Xie X AD - Shanghai TCM-Integrated hospital (endocrinology department), Shanghai, China. FAU - Chen, Ying AU - Chen Y AD - Department of Endocrinology and Metabolism, Center for Microbiota and Immunological Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Lin, Yi AU - Lin Y AD - Department of Endocrinology and Metabolism, Center for Microbiota and Immunological Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Cai, Zhaogen AU - Cai Z AD - Department of Pathology, the First Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, Anhui, China. FAU - Ding, Li AU - Ding L AD - Department of Pathology, the First Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, Anhui, China. FAU - Wu, Yijie AU - Wu Y AD - Department of Endocrinology and Metabolism, Center for Microbiota and Immunological Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Peng, Yongde AU - Peng Y AD - Department of Endocrinology and Metabolism, Center for Microbiota and Immunological Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Tang, Shanshan AU - Tang S AD - Department of Endocrinology and Metabolism, Center for Microbiota and Immunological Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Xu, Huanbai AU - Xu H AD - Department of Endocrinology and Metabolism, Center for Microbiota and Immunological Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Antineoplastic Agents, Hormonal) RN - 0 (CXCL12 protein, human) RN - 0 (CXCR4 protein, human) RN - 0 (Chemokine CXCL12) RN - 0 (ESR1 protein, human) RN - 0 (Estrogen Receptor alpha) RN - 0 (PPAR gamma) RN - 0 (PPARG protein, human) RN - 0 (Receptors, CXCR4) RN - 094ZI81Y45 (Tamoxifen) SB - IM MH - Animals MH - Antineoplastic Agents, Hormonal/*pharmacology/therapeutic use MH - Carcinogenesis/drug effects/genetics/*pathology MH - Cell Line, Tumor MH - Cell Movement/drug effects/genetics MH - Cell Proliferation/drug effects/genetics MH - Chaperone-Mediated Autophagy/drug effects/genetics/*physiology MH - Chemokine CXCL12/metabolism MH - Datasets as Topic MH - Disease Progression MH - Estrogen Receptor alpha/antagonists & inhibitors/genetics/*metabolism MH - Female MH - Gene Knockdown Techniques MH - Humans MH - Male MH - Mice MH - Middle Aged MH - PPAR gamma/metabolism MH - Receptors, CXCR4/metabolism MH - Signal Transduction/drug effects/genetics MH - Tamoxifen/pharmacology/therapeutic use MH - Thyroid Cancer, Papillary/drug therapy/*pathology/surgery MH - Thyroid Gland/pathology/surgery MH - Thyroid Neoplasms/drug therapy/*pathology/surgery MH - Thyroidectomy MH - Xenograft Model Antitumor Assays OTO - NOTNLM OT - PPARgamma OT - SDF1/CXCR4 signaling OT - chaperone-mediated autophagy OT - papillary thyroid carcinoma EDAT- 2020/06/20 06:00 MHDA- 2021/02/20 06:00 CRDT- 2020/06/20 06:00 PHST- 2019/12/26 00:00 [received] PHST- 2020/06/14 00:00 [accepted] PHST- 2020/06/20 06:00 [pubmed] PHST- 2021/02/20 06:00 [medline] PHST- 2020/06/20 06:00 [entrez] AID - 5859150 [pii] AID - 10.1210/clinem/dgaa366 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2020 Oct 1;105(10):dgaa366. doi: 10.1210/clinem/dgaa366.