Elevated expression of myosin X in tumours contributes to breast cancer aggressiveness and metastasis.
Elevated expression of myosin X in tumours contributes to breast cancer aggressiveness and metastasis.
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肿瘤中肌球蛋白 X 的表达升高有助于乳腺癌的侵袭性和转移
DOI：
10.1038/bjc.2014.298
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发表时间：
2014-07-29
影响因子：
8.8
通讯作者：
Zhu, X.
中科院分区：
文献类型：
--
作者：
Cao, R.;Chen, J.;Zhang, X.;Zhai, Y.;Qing, X.;Xing, W.;Zhang, L.;Malik, Y. S.;Yu, H.;Zhu, X.
背景：最近有报道称，MYO10在乳腺癌中通过将整合素转运到丝状尖端来促进肿瘤侵袭。然而，MYO10在肿瘤中的作用仍不明确。本文中，我们报道了MYO10在侵入性植物中介导侵袭性生长和细胞外基质降解是必需的，这取决于MYO10的pleckstrin同源结构域与PtdIns (3,4,5) P3的结合。方法：在乳腺癌细胞和乳腺癌标本（n= 120）中检测MYO10的表达及其与临床病理和生物学因素的关系。对MYO10沉默后的细胞迁移和侵袭进行了研究。利用异硫氰酸荧光素偶联明胶降解测定法研究了细胞形成侵入样体的能力。建立小鼠模型，研究肿瘤在体内的侵袭性生长和转移。结果：MYO10水平升高与雌激素受体状态、孕激素受体状态、分化不良、淋巴结转移相关。沉默MYO10可减少细胞迁移和侵袭。MYO10促进入侵的作用是由Invadopodia引起的。此外，在myo10沉默的裸鼠模型中观察到侵袭性生长和肺转移的减少。结论：我们的研究结果表明，MYO10表达升高会增加乳腺癌的侵袭性；这种作用依赖于MYO10参与侵殖形成。
Background:Myosin X (MYO10) was recently reported to promote tumour invasion by transporting integrins to filopodial tips in breast cancer. However, the role of MYO10 in tumours remains poorly defined. Here, we report that MYO10 is required in invadopodia to mediate invasive growth and extracellular matrix degradation, which depends on the binding of MYO10’s pleckstrin homology domain to PtdIns (3, 4, 5) P3.Methods:The expression of MYO10 and its associations with clinicopathological and biological factors were examined in breast cancer cells and breast cancer specimens (n= 120). Cell migration and invasion were investigated after the silencing of MYO10. The ability of cells to form invadopodia was studied using a fluorescein isothiocyanate-conjugated gelatin degradation assay. A mouse model was established to study tumour invasive growth and metastasis in vivo.Results:Elevated MYO10 levels were correlated with oestrogen receptor status, progesterone receptor status, poor differentiation, and lymph node metastasis. Silencing MYO10 reduced cell migration and invasion. Invadopodia were responsible for MYO10’s role in promoting invasion. Furthermore, decreased invasive growth and lung metastasis were observed in the MYO10-silenced nude mouse model.Conclusions:Our findings suggest that elevated MYO10 expression increases the aggressiveness of breast cancer; this effect is dependent on the involvement of MYO10 in invadopodial formation.
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影响因子：
8.8
作者：
Akanuma, N.;Hoshino, I.;Akutsu, Y.;Murakami, K.;Isozaki, Y.;Maruyama, T.;Yusup, G.;Qin, W.;Toyozumi, T.;Takahashi, M.;Suito, H.;Hu, X.;Sekino, N.;Matsubara, H.
通讯作者：
Matsubara, H.
影响因子：
3.2
作者：
Arjonen, Antti;Kaukonen, Riina;Ivaska, Johanna
通讯作者：
Ivaska, Johanna
影响因子：
7.5
作者：
Gimona, Mario;Buccione, Roberto;Linder, Stefan
通讯作者：
Linder, Stefan
影响因子：
168.9
作者：
Gianni, Luca;Eiermann, Wolfgang;Baselga, Jose
通讯作者：
Baselga, Jose
影响因子：
8
作者：
Cermak, Vladimir;Kosla, Jan;Dvorak, Michal
通讯作者：
Dvorak, Michal