Cell aggregation induces phosphorylation of PECAM-1 and Pyk2 and promotes tumor cell anchorage-independent growth
Cell aggregation induces phosphorylation of PECAM-1 and Pyk2 and promotes tumor cell anchorage-independent growth
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细胞聚集诱导 PECAM-1 和 Pyk2 磷酸化并促进肿瘤细胞贴壁依赖性生长
DOI：
10.1186/1476-4598-9-7
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发表时间：
2010-01
期刊：
影响因子：
--
通讯作者：
Xing Zhang
中科院分区：
文献类型：
--
作者：
Li-hua Xu;俞强;Xing Zhang
研究背景细胞与基质相互作用不足或不适当引起的细胞凋亡称为失巢凋亡。虽然已知转化细胞是抗失巢凋亡的，但其潜在机制尚未得到很好的理解。我们研究了肿瘤细胞抗失巢凋亡的机制。ResultsWe观察到，悬浮的细胞聚集促进细胞存活和增殖。我们证明了肿瘤细胞在悬浮液中的聚集和软琼脂中的细胞生长之间的相关性。酪氨酸激酶介导的细胞存活和生长信号传导途径的分析揭示了细胞聚集体中PECAM-1和Pyk 2的酪氨酸磷酸化水平增加。我们还发现PECAM-1和Pyk 2相互作用，并且携带外显子11-16缺失的PECAM-1不再与Pyk 2结合。此外，RNA干扰介导的Pyk 2和PECAM-1蛋白水平的降低减少了细胞聚集并抑制了肿瘤细胞在软琼脂中的生长。结论数据表明，Pyk 2和PECAM-1是肿瘤细胞锚定非依赖性生长和抗失巢凋亡的关键介质。
BackgroundApoptosis caused by inadequate or inappropriate cell-matrix interactions is defined as anoikis. Although transformed cells are known to be anoikis-resistant, the underlying mechanisms have not been well understood. We investigated the mechanisms of anoikis resistance of tumor cells.ResultsWe observed that cell aggregation in suspension promoted cell survival and proliferation. We demonstrated a correlation between tumor cell aggregation in suspension and cell growth in soft agar. Analysis of tyrosine kinase-mediated cell survival and growth signaling pathways revealed increased levels of tyrosine-phosphorylation of PECAM-1 and Pyk2 in cell aggregates. We also showed that PECAM-1 and Pyk2 physically interact with each other, and that PECAM-1 carrying a deletion of exons 11-16 could no longer bind to Pyk2. Furthermore, RNA interference-mediated reduction of Pyk2 and PECAM-1 protein levels reduced cell aggregation and inhibited the growth of tumor cells in soft agar.ConclusionsThe data demonstrated that Pyk2 and PECAM-1 were critical mediators of both anchorage-independent growth and anoikis resistance in tumor cells.
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DOI：
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发表时间：
2009
期刊：
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影响因子：
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作者：
Xiaowei Sun;R. Essalmani;N. Seidah;A. Prat
通讯作者：
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影响因子：
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通讯作者：
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DOI：
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发表时间：
2002-02
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
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DOI：
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发表时间：
2004
期刊：
The Journal of biological chemistry
影响因子：
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作者：
Yan Zhang;Hai Lu;P. Dazin;Y. Kapila
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Yan Zhang;Hai Lu;P. Dazin;Y. Kapila