Solute carrier family 35 member F2 is indispensable for papillary thyroid carcinoma progression through activation of transforming growth factor-β type I receptor/apoptosis signal-regulating kinase 1/mitogen-activated protein kinase signaling axis.
Solute carrier family 35 member F2 is indispensable for papillary thyroid carcinoma progression through activation of transforming growth factor-β type I receptor/apoptosis signal-regulating kinase 1/mitogen-activated protein kinase signaling axis.
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溶质载体家族 35 成员 F2 通过激活转化生长因子 I 型受体/凋亡信号调节激酶 1/丝裂原激活蛋白激酶信号轴，对于甲状腺乳头状癌的进展是不可或缺的
DOI：
10.1111/cas.13478
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发表时间：
2018-03
期刊：
影响因子：
5.7
通讯作者：
Zou Q
中科院分区：
文献类型：
--
作者：
He J;Jin Y;Zhou M;Li X;Chen W;Wang Y;Gu S;Cao Y;Chu C;Liu X;Zou Q
溶质载体家族成员控制着基本的生理功能，并与人类疾病密切相关。溶质载体家族35成员F2 （SLC35F2）在几种恶性肿瘤中异常激活。然而，SLC35F2在甲状腺乳头状癌（PTC）中的生物学功能和分子机制尚未得到充分探讨。在这里，我们发现SLC35F2在PTC组织中的蛋白和mRNA表达水平与匹配的邻近正常组织相比均显著上调。此外，SLC35F2的高表达与PTC患者的淋巴结转移有显著相关性。CRISPR/Cas9介导的SLC35F2敲除降低了PTC的致瘤性，包括细胞增殖、迁移和侵袭以及诱导G1期阻滞。相反，SLC35F2的异位表达导致PTC细胞具有侵袭性恶性表型。此外，SLC35F2通过靶向转化生长因子β I型受体（TGFBR1）和磷酸化凋亡信号调节激酶1 (p‐ASK‐1)，从而激活丝裂原激活的蛋白激酶信号通路，加速PTC细胞的增殖和迁移。通过使用特异性抑制剂沉默TGFBR1，可以消除SLC35F2过表达诱导的恶性行为。我们首次开展了SLC35F2在甲状腺癌中的研究，旨在阐明SLC35F2的功能意义和分子机制。我们的研究结果表明，SLC35F2通过丝裂原激活蛋白激酶途径对PTC进展发挥其致癌作用，依赖于TGFBR - 1和凋亡信号调节激酶1的激活。
Solute carrier family members control essential physiological functions and are tightly linked to human diseases. Solute carrier family 35 member F2 (SLC35F2) is aberrantly activated in several malignancies. However, the biological function and molecular mechanism of SLC35F2 in papillary thyroid carcinoma (PTC) are yet to be fully explored. Here, we showed that SLC35F2 was prominently upregulated in PTC tissues at both protein and mRNA expression level compared with matched adjacent normal tissues. Besides, the high expression of SLC35F2 was significantly associated with lymph node metastasis in patients with PTC. CRISPR/Cas9‐mediated knockout of SLC35F2 attenuated the tumorigenic properties of PTC, including cell proliferation, migration and invasion and induced G1 phase arrest. In contrast, ectopic expression of SLC35F2 brought about aggressive malignant phenotypes of PTC cells. Moreover, SLC35F2 expedited the proliferation and migration of PTC cells by targeting transforming growth factor‐β type I receptor (TGFBR1) and phosphorylation of apoptosis signal‐regulating kinase 1 (p‐ASK‐1), thereby activating the mitogen‐activated protein kinase signaling pathway. The malignant behaviors induced by overexpression of SLC35F2 could be abrogated by silencing of TGFBR1 using a specific inhibitor. We conducted the first study on SLC35F2 in thyroid cancer with the aim of elucidating the functional significance and molecular mechanism of SLC35F2. Our findings suggest that SLC35F2 exerts its oncogenic effect on PTC progression through the mitogen‐activated protein kinase pathway, with dependence on activation of TGFBR‐1 and apoptosis signal‐regulating kinase 1.
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影响因子：
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