論文 - 詳細
| RRC ID | 64920 |
|---|---|
| 著者 | Tanaka M, Shimamura S, Kuriyama S, Maeda D, Goto A, Aiba N. |
| タイトル | SKAP2 Promotes Podosome Formation to Facilitate Tumor-Associated Macrophage Infiltration and Metastatic Progression. |
| ジャーナル | Cancer Res |
| Abstract |
Tumor-associated macrophages (TAM) play complex and pivotal roles during cancer progression. A subset of metastasis-associated macrophages accumulates within metastatic sites to promote the invasion and growth of tumor cells. Src kinase-associated phosphoprotein 2 (SKAP2), a substrate of Src family kinases, is highly expressed in macrophages from various tumors, but its contribution to the tumor-promoting behavior of TAMs is unknown. Here, we report that SKAP2 regulates podosome formation in macrophages to promote tumor invasion and metastasis. SKAP2 physically interacted with Wiskott-Aldrich syndrome protein (WASP) and localized to podosomes, which were rarely observed in SKAP2-null macrophages. The invasion of peritoneal macrophages derived from SKAP2-null mice was significantly reduced compared with wild-type macrophages, but could be rescued by the restoration of functional SKAP2 containing an intact tyrosine phosphorylation site and the ability to interact with WASP. Furthermore, SKAP2-null mice inoculated with lung cancer cells exhibited markedly decreased lung metastases characterized by reduced macrophage infiltration compared with wild-type mice. Moreover, intravenously injected SKAP2-null macrophages failed to efficiently infiltrate established tumors and promote their growth. Taken together, these findings reveal a novel mechanism by which macrophages assemble the appropriate motile machinery to infiltrate tumors and promote disease progression, and implicate SKAP2 as an attractive candidate for therapeutically targeting TAMs. |
| 巻・号 | 76(2) |
| ページ | 358-69 |
| 公開日 | 2016-1-15 |
| DOI | 10.1158/0008-5472.CAN-15-1879 |
| PII | 0008-5472.CAN-15-1879 |
| PMID | 26577701 |
| MeSH | Animals Breast Neoplasms / metabolism Breast Neoplasms / pathology Carcinoma, Lewis Lung / metabolism Carcinoma, Lewis Lung / pathology Cell Line, Tumor Disease Progression Female Humans Intracellular Signaling Peptides and Proteins / metabolism* Macrophages / metabolism Macrophages / pathology* Macrophages, Peritoneal / metabolism Macrophages, Peritoneal / pathology Melanoma, Experimental / metabolism Melanoma, Experimental / pathology Mice Mice, Inbred C57BL Mice, Knockout Neoplasm Metastasis Podosomes / genetics Podosomes / metabolism Podosomes / pathology* RAW 264.7 Cells |
| IF | 9.727 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | LLC(RCB0558) |