PMID- 29940537 OWN - NLM STAT- MEDLINE DCOM- 20181218 LR - 20210503 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 106 DP - 2018 Oct TI - CPT1A regulates breast cancer-associated lymphangiogenesis via VEGF signaling. PG - 1-7 LID - S0753-3322(18)30380-9 [pii] LID - 10.1016/j.biopha.2018.05.112 [doi] AB - BACKGROUND: Lymphangiogenesis is critical for metastasis of a variety of cancers, including breast cancer. CPT1A (carnitine palmitoyltransferase 1a) has been reported to play a critical role in breast cancer progress. However, the molecular mechanism remains elusive. METHODS: In order to investigate the role of CPT1A in HDLEC cells, short hairpin RNA approach was utilized to knock down the CPT1A gene expression. We employed transwell and lymphatic vessel formation assay to examine invasion and lymphangiogenesis of HDLEC (Human dermal lymphatic endothelial cells). RT-qPCR and westernblot analyses were used to determine genes expression in HDLEC and breast cancer cells. Finally, we determined the relative rate of acetyl-CoA/CoA in shNC and shCPT1A HDLEC cells by LC-MS approach. RESULTS: Knockdown of CPT1A in breast cancer cells (MCF-7 and MDA-MB-231) abolished invasion and lymphangiogenesis of HDLEC cells. Mechanistically, CPT1A depletion suppressed the expression of VEGF-C and VEGF-D in MCF-7 and MDA-MB-231 cells. Interestingly, CPT1A knockdown in HDLEC cells exhibited attenuated expression of lymphangiogenic markers (podoplanin, VEGFR-3, VEGF-C, VEGF-D and PROX-1). Consistently, CPT1A -null HDLEC cells displayed compromised invasion and lymphangiogenesis compared with negative control. Further investigation revealed that CPT1A regulated VEGFR3 via acetyl-CoA mediated H3K9ac, which could be abrogated by supplement of acetate. CONCLUSIONS: In present study, we revealed the mechanism by which CPT1A regulates breast cancer-associated invasion and lymphangiogenesis. Our findings provide insights into CPT1A -promoted breast tumor metastasis and provide rationale for understanding breast cancer metastasis. CI - Copyright (c) 2018. Published by Elsevier Masson SAS. FAU - Xiong, Yiquan AU - Xiong Y AD - Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China. FAU - Liu, Zeming AU - Liu Z AD - Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China. FAU - Zhao, Xiangwang AU - Zhao X AD - Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China. FAU - Ruan, Shengnan AU - Ruan S AD - Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China. FAU - Zhang, Ximeng AU - Zhang X AD - Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China. FAU - Wang, Shi AU - Wang S AD - Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China. FAU - Huang, Tao AU - Huang T AD - Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China. Electronic address: huangtao180117@sina.com. LA - eng PT - Journal Article DEP - 20180623 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (VEGFC protein, human) RN - 0 (VEGFD protein, human) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (Vascular Endothelial Growth Factor C) RN - 0 (Vascular Endothelial Growth Factor D) RN - 72-89-9 (Acetyl Coenzyme A) RN - EC 2.3.1.21 (CPT1A protein, human) RN - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase) RN - EC 2.7.10.1 (FLT4 protein, human) RN - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-3) SB - IM MH - Acetyl Coenzyme A/metabolism MH - Acetylation MH - Breast Neoplasms/*enzymology/genetics/pathology MH - Carnitine O-Palmitoyltransferase/genetics/*metabolism MH - Cell Communication MH - Cell Movement MH - Coculture Techniques MH - Endothelial Cells/*enzymology/pathology MH - Endothelium, Lymphatic/*enzymology/pathology MH - Gene Expression Regulation, Enzymologic MH - Gene Expression Regulation, Neoplastic MH - Humans MH - *Lymphangiogenesis/genetics MH - MCF-7 Cells MH - Neoplasm Metastasis MH - *Signal Transduction MH - Vascular Endothelial Growth Factor A/genetics/*metabolism MH - Vascular Endothelial Growth Factor C/genetics/metabolism MH - Vascular Endothelial Growth Factor D/genetics/metabolism MH - Vascular Endothelial Growth Factor Receptor-3/genetics/metabolism OTO - NOTNLM OT - CPT1A OT - Lymphangiogenesis OT - VEGF-C and VEGF-D OT - VEGFR-3 EDAT- 2018/06/26 06:00 MHDA- 2018/12/19 06:00 CRDT- 2018/06/26 06:00 PHST- 2018/01/17 00:00 [received] PHST- 2018/05/22 00:00 [revised] PHST- 2018/05/23 00:00 [accepted] PHST- 2018/06/26 06:00 [pubmed] PHST- 2018/12/19 06:00 [medline] PHST- 2018/06/26 06:00 [entrez] AID - S0753-3322(18)30380-9 [pii] AID - 10.1016/j.biopha.2018.05.112 [doi] PST - ppublish SO - Biomed Pharmacother. 2018 Oct;106:1-7. doi: 10.1016/j.biopha.2018.05.112. Epub 2018 Jun 23.