論文 - 詳細
| RRC ID | 47446 |
|---|---|
| 著者 | Wolfe AR, Ernlund A, McGuinness W, Lehmann C, Carl K, Balmaceda N, Neufeld KL. |
| タイトル | Suppression of intestinal tumorigenesis in Apc mutant mice upon Musashi-1 deletion. |
| ジャーナル | J Cell Sci |
| Abstract |
Therapeutic strategies based on a specific oncogenic target are better justified when elimination of that particular oncogene reduces tumorigenesis in a model organism. One such oncogene, Musashi-1 (Msi-1), regulates translation of target mRNAs and is implicated in promoting tumorigenesis in the colon and other tissues. Msi-1 targets include the tumor suppressor adenomatous polyposis coli (Apc), a Wnt pathway antagonist lost in ∼80% of all colorectal cancers. Cell culture experiments have established that Msi-1 is a Wnt target, thus positioning Msi-1 and Apc as mutual antagonists in a mutually repressive feedback loop. Here, we report that intestines from mice lacking Msi-1 display aberrant Apc and Msi-1 mutually repressive feedback, reduced Wnt and Notch signaling, decreased proliferation, and changes in stem cell populations, features predicted to suppress tumorigenesis. Indeed, mice with germline Apc mutations (ApcMin ) or with the Apc1322T truncation mutation have a dramatic reduction in intestinal polyp number when Msi-1 is deleted. Taken together, these results provide genetic evidence that Msi-1 contributes to intestinal tumorigenesis driven by Apc loss, and validate the pursuit of Msi-1 inhibitors as chemo-prevention agents to reduce tumor burden. |
| 巻・号 | 130(4) |
| ページ | 805-813 |
| 公開日 | 2017-2-15 |
| DOI | 10.1242/jcs.197574 |
| PII | jcs.197574 |
| PMID | 28082422 |
| PMC | PMC5339888 |
| MeSH | Adenomatous Polyposis Coli / genetics* Animals Carcinogenesis / metabolism* Carcinogenesis / pathology* Cell Count Cell Proliferation Colonic Polyps / metabolism Colonic Polyps / pathology Disease Models, Animal Epithelium / metabolism Epithelium / pathology Gene Deletion* Intestinal Neoplasms / metabolism* Intestinal Neoplasms / pathology* Intestine, Small / metabolism Intestine, Small / pathology Mice Mice, Mutant Strains Nerve Tissue Proteins / genetics* Nerve Tissue Proteins / metabolism RNA-Binding Proteins / genetics* RNA-Binding Proteins / metabolism Receptors, Notch / metabolism Stem Cells / metabolism Wnt Signaling Pathway |
| IF | 4.573 |
| 引用数 | 4 |
| WOS 分野 | CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | Blogs |
| 各媒体での言及数の合計 | 3 |
| 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 | |
| 実験動物マウス | RBRC04435 |