Lysosomal protein transmembrane 5 promotes lung-specific metastasis by regulating BMPR1A lysosomal degradation.
Lysosomal protein transmembrane 5 promotes lung-specific metastasis by regulating BMPR1A lysosomal degradation.
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DOI：
10.1038/s41467-022-31783-6
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发表时间：
2022-07-16
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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作者：
在癌症转移过程中，向器官性经常发生，但其潜在机制仍知之甚少。在这里，我们表明，溶酶体蛋白跨膜5（LAPTM 5）促进肾癌的肺特异性转移。LAPTM 5通过阻断肺源性骨形态发生蛋白（BMP）的功能来维持肾癌细胞的自我更新和癌症干细胞样特征。机制研究表明，LAPTM 5招募WWP2，其结合BMP受体BMPR1A并介导其溶酶体分选，泛素化和最终降解。BMPR1A表达通过溶酶体抑制剂氯喹恢复。LAPTM5表达也可作为肾癌肺转移的独立预测因子。最后，肺转移中LAPTM 5表达的升高是多种癌症类型中的常见现象。我们的研究结果揭示了肺特异性转移的分子机制，并确定LAPTM 5作为肺转移癌症的潜在治疗靶点。肾细胞癌（RCC）肺特异性转移的机制仍有待详细研究。在这里，作者表明，LAPTM 5通过抑制BMP信号传导，从而增强RCC的自我更新和癌症干细胞样特征，有助于RCC的肺特异性转移。
Organotropism during cancer metastasis occurs frequently but the underlying mechanism remains poorly understood. Here, we show that lysosomal protein transmembrane 5 (LAPTM5) promotes lung-specific metastasis in renal cancer. LAPTM5 sustains self-renewal and cancer stem cell-like traits of renal cancer cells by blocking the function of lung-derived bone morphogenetic proteins (BMPs). Mechanistic investigations showed that LAPTM5 recruits WWP2, which binds to the BMP receptor BMPR1A and mediates its lysosomal sorting, ubiquitination and ultimate degradation. BMPR1A expression was restored by the lysosomal inhibitor chloroquine. LAPTM5 expression could also serve as an independent predictor of lung metastasis in renal cancer. Lastly, elevation of LAPTM5 expression in lung metastases is a common phenomenon in multiple cancer types. Our results reveal a molecular mechanism underlying lung-specific metastasis and identify LAPTM5 as a potential therapeutic target for cancers with lung metastasis. The mechanisms that confer lung-specific metastasis in renal cell carcinomas (RCC) remain to be detailed. Here the authors show that LAPTM5 contributes to lung-specific metastasis of RCCs by suppressing BMP signalling and thus, enhancing self-renewal and cancer stem cell-like traits of RCCs.
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DOI：
10.1158/1078-0432.ccr-13-3227
发表时间：
2014-06-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Cook KL;Wärri A;Soto-Pantoja DR;Clarke PA;Cruz MI;Zwart A;Clarke R
通讯作者：
Clarke R
影响因子：
64.8
作者：
通讯作者：
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影响因子：
3.8
作者：
Arnaout, Angel;Robertson, Susan J.;Clemons, Mark
通讯作者：
Clemons, Mark
DOI：
10.1158/1078-0432.ccr-18-2204
发表时间：
2019-04-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Haas NB;Appleman LJ;Stein M;Redlinger M;Wilks M;Xu X;Onorati A;Kalavacharla A;Kim T;Zhen CJ;Kadri S;Segal JP;Gimotty PA;Davis LE;Amaravadi RK
通讯作者：
Amaravadi RK
影响因子：
4.8
作者：
Harvey, KF;Dinudom, A;Kumar, S
通讯作者：
Kumar, S