SLC34A2 simultaneously promotes papillary thyroid carcinoma growth and invasion through distinct mechanisms.

Autor: He J; Department of General Surgery, Huashan Hospital, Fudan University, 12 Urumqi Middle Road, Shanghai, 200040, China., Zhou M; Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, Shanghai, 200092, China., Li X; Department of General Surgery, Huashan Hospital, Fudan University, 12 Urumqi Middle Road, Shanghai, 200040, China., Gu S; Department of General Surgery, Huashan Hospital, Fudan University, 12 Urumqi Middle Road, Shanghai, 200040, China., Cao Y; Department of General Surgery, Huashan Hospital, Fudan University, 12 Urumqi Middle Road, Shanghai, 200040, China., Xing T; Department of General Surgery, Huashan Hospital, Fudan University, 12 Urumqi Middle Road, Shanghai, 200040, China., Chen W; Department of General Surgery, Huashan Hospital, Fudan University, 12 Urumqi Middle Road, Shanghai, 200040, China., Chu C; Department of General Surgery, Huashan Hospital, Fudan University, 12 Urumqi Middle Road, Shanghai, 200040, China., Gu F; Department of General Surgery, Huashan Hospital, Fudan University, 12 Urumqi Middle Road, Shanghai, 200040, China., Zhou J; Department of General Surgery, Huashan Hospital, Fudan University, 12 Urumqi Middle Road, Shanghai, 200040, China., Jin Y; Department of General Surgery, Huashan Hospital, Fudan University, 12 Urumqi Middle Road, Shanghai, 200040, China., Ma J; Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences and Institute of Biomedical Sciences, Fudan University, 130 Dong'an Road, Shanghai, 200032, China., Ma D; Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences and Institute of Biomedical Sciences, Fudan University, 130 Dong'an Road, Shanghai, 200032, China. duanma@fudan.edu.cn., Zou Q; Department of General Surgery, Huashan Hospital, Fudan University, 12 Urumqi Middle Road, Shanghai, 200040, China. zouqiang_hs@163.com.
Jazyk: angličtina
Zdroj: Oncogene [Oncogene] 2020 Mar; Vol. 39 (13), pp. 2658-2675. Date of Electronic Publication: 2020 Jan 31.
DOI: 10.1038/s41388-020-1181-z
Abstrakt: Thyroid cancer is the fastest growing cancer among all solid tumors in recent decades. Papillary thyroid carcinoma (PTC) is the most predominant type of thyroid cancer. Around 30% of PTC patients with distant metastases and local invasion receive poor prognosis. Thus, the identification of new druggable biological targets is of great importance. Accumulating evidence indicates that solute carrier family numbers have emerged as obligate effectors during the progression of multiple malignancies. Here, we uncovered the functional significance, molecular mechanisms, and clinical impact of solute carrier family 34 member A2 (SLC34A2) in PTC. SLC34A2 was markedly overexpressed in PTC tissues at both mRNA and protein levels compared with matched adjacent normal tissues due to promoter hypomethylation mediated by the DNA methyltransferase 3 beta (DNMT3B). Furthermore, a series of in vivo and in vitro gain- or loss-of-functional assays elucidated the role of SLC34A2 in boosting cell proliferation, cell cycle progression, migration, invasion, and adhesion of PTC cells. Using immunoprecipitation and mass spectrometry, we discovered that SLC34A2 bound to the actin-binding repeats domain of Cortactin (CTTN), thereby inducing the invadopodia formation of PTC cells to promote the metastasis potential of PTC cells. Besides, our mechanistic studies, as well as gene set enrichment analysis (GSEA), have pinpointed the PTEN/AKT/FOXO3a pathway as a major signaling functioning downstream of SLC34A2 regulated cell growth. Taken together, our results highlighted that SLC34A2 plays a pivotal oncogenic role during carcinogenesis and metastasis through distinct mechanisms in PTC.
Databáze: MEDLINE
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