StarD13 negatively regulates invadopodia formation and invasion in high-grade serous (HGS) ovarian adenocarcinoma cells by inhibiting Cdc42.
StarD13 negatively regulates invadopodia formation and invasion in high-grade serous (HGS) ovarian adenocarcinoma cells by inhibiting Cdc42.
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DOI：
10.1016/j.ejcb.2021.151197
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发表时间：
2022-01
影响因子：
6.6
通讯作者：
El-Sibai M
中科院分区：
文献类型：
--
作者：
Abdellatef S;Fakhoury I;Haddad MA;Jaafar L;Maalouf H;Hanna S;Khalil B;El Masri Z;Hodgson L;El-Sibai M
转移仍然是治疗卵巢癌的主要挑战。在这项研究中，我们研究了Cdc42 GAP StarD13在调节卵巢癌细胞运动性和侵袭性中的潜在作用。StarD13缺失不影响卵巢癌细胞的2D运动性。更重要的是，StarD13通过抑制Cdc42抑制基质降解、侵袭伪足形成和细胞侵袭。StarD13不定位于具有基质降解能力的成熟TKS 4标记的侵袭伪足，而Cdc42 FRET生物传感器检测这些侵袭伪足中的Cdc42活化。事实上，StarD13定位和Cdc42激活在侵入伪足结构中似乎是相互排斥的。最后，我们首次发现了Cdc 42在直接招募TKS 4至侵袭伪足中的潜在作用。这项研究强调了StarD13作为Cdc42的狭窄空间调节剂的特定作用，抑制侵袭，表明StarD13适用于靶向治疗。
Metastasis remains the main challenge to overcome for treating ovarian cancers. In this study, we investigate the potential role of the Cdc42 GAP StarD13 in the modulation of cell motility, invasion in ovarian cancer cells. StarD13 depletion does not affect the 2D motility of ovarian cancer cells. More importantly, StarD13 inhibits matrix degradation, invadopodia formation and cell invasion through the inhibition of Cdc42. StarD13 does not localize to mature TKS4-labeled invadopodia that possess matrix degradation ability, while a Cdc42 FRET biosensor, detects Cdc42 activation in these invadopodia. In fact, StarD13 localization and Cdc42 activation appear mutually exclusive in invadopodial structures. Finally, for the first time we uncover a potential role of Cdc42 in the direct recruitment of TKS4 to invadopodia. This study emphasizes the specific role of StarD13 as a narrow spatial regulator of Cdc42, inhibiting invasion, suggesting the suitability of StarD13 for targeted therapy.
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影响因子：
8.4
作者：
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通讯作者：
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影响因子：
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