SIK2通过磷酸化MYLK促进卵巢癌细胞运动和转移,Molecular Oncology

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SIK2通过磷酸化MYLK促进卵巢癌细胞运动和转移
Molecular Oncology ( IF 5.0 ) Pub Date : 2022-03-12 , DOI: 10.1002/1878-0261.13208
Xiu Shi _{1,

2,

3} , Xuejiao Yu ₄ , Juan Wang ₁ , Shimin Bian ₁ , Qiutong Li ₁ , Fengqing Fu _{2,

3} , Xinwei Zou ₁ , Lin Zhang ₁ , Robert C Bast ₅ , Zhen Lu ₅ , Lingchuan Guo ₆ , Youguo Chen _{1,

2} , Jinhua Zhou _{1,

2}

Affiliation

盐诱导激酶 2（SIK2；也称为丝氨酸/苏氨酸蛋白激酶 SIK2）在几种癌症中过度表达，并与癌症进展有关。然而，SIK2在卵巢癌中调节癌细胞运动、迁移和转移的机制尚未完全被发现。在这里，我们发现 SIK2在体外和体内促进卵巢癌细胞运动、迁移和转移. 从机制上讲，SIK2 通过肌球蛋白轻链激酶、平滑肌 (MYLK) 介导的肌球蛋白轻链 2 (MYL2) 的磷酸化调节癌细胞的运动和迁移。SIK2 在 Ser343 位点直接磷酸化 MYLK 并激活其下游效应子 MYL2，促进卵巢癌细胞的运动和转移。此外，我们发现脂肪细胞在 Ser358 处诱导 SIK2 磷酸化，在 Ser343 处诱导 MYLK 磷酸化，从而增强卵巢癌细胞的运动性。此外，SIK2蛋白表达与卵巢癌细胞系和组织中MYLK-pS343的表达呈正相关。SIK2 和 MYLK-pS343 的共表达与人类卵巢癌样本的中位总生存期降低有关。总之，SIK2 正向调节卵巢癌的运动、迁移和转移，

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SIK2 promotes ovarian cancer cell motility and metastasis by phosphorylating MYLK

Salt-inducible kinase 2 (SIK2; also known as serine/threonine-protein kinase SIK2) is overexpressed in several cancers and has been implicated in cancer progression. However, the mechanisms by which SIK2 regulates cancer cell motility, migration and metastasis in ovarian cancer have not been fully discovered. Here, we identify that SIK2 promotes ovarian cancer cell motility, migration and metastasis in vitro and in vivo. Mechanistically, SIK2 regulated cancer cell motility and migration by myosin light chain kinase, smooth muscle (MYLK)-meditated phosphorylation of myosin light chain 2 (MYL2). SIK2 directly phosphorylated MYLK at Ser343 and activated its downstream effector MYL2, promoting ovarian cancer cell motility and metastasis. In addition, we found that adipocytes induced SIK2 phosphorylation at Ser358 and MYLK phosphorylation at Ser343, enhancing ovarian cancer cell motility. Moreover, SIK2 protein expression was positively correlated with the expression of MYLK-pS343 in ovarian cancer cell lines and tissues. The co-expression of SIK2 and MYLK-pS343 was associated with reduced median overall survival in human ovarian cancer samples. Taken together, SIK2 positively regulates ovarian cancer motility, migration and metastasis, suggesting that SIK2 is a potential candidate for ovarian cancer treatment.

更新日期：2022-03-12

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