EMT programs promote basal mammary stem cell and tumor-initiating cell stemness by inducing primary ciliogenesis and Hedgehog signaling
Tissue regeneration relies on adult stem cells (SCs) that possess the ability to self-renew and produce differentiating progeny. In an analogous manner, the development of certain carcinomas depends on a small subset of tumor cells, called “tumor-initiating cells” (TICs), with SC-like properties. Ma...
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National Academy of Sciences (U.S.)
2018
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| Online Access: | http://hdl.handle.net/1721.1/116331 https://orcid.org/0000-0003-2175-4066 https://orcid.org/0000-0002-0895-3557 https://orcid.org/0000-0001-9451-2194 |
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| author | Kröger, Cornelia Ye, Xin Guen, Vincent Chavarria, Tony E Weinberg, Robert A Lees, Jacqueline |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Kröger, Cornelia Ye, Xin Guen, Vincent Chavarria, Tony E Weinberg, Robert A Lees, Jacqueline |
| author_sort | Kröger, Cornelia |
| collection | MIT |
| description | Tissue regeneration relies on adult stem cells (SCs) that possess the ability to self-renew and produce differentiating progeny. In an analogous manner, the development of certain carcinomas depends on a small subset of tumor cells, called “tumor-initiating cells” (TICs), with SC-like properties. Mammary SCs (MaSCs) reside in the basal compartment of the mammary epithelium, and their neoplastic counterparts, mammary TICs (MaTICs), are thought to serve as the TICs for the claudin-low subtype of breast cancer. MaSCs and MaTICs both use epithelial–mesenchymal transition (EMT) programs to acquire SC properties, but the mechanism(s) connecting EMT programs to stemness remain unclear. Here we show that this depends on primary cilia, which are nonmotile, cell-surface structures that serve as platforms for receiving cues and enable activation of various signaling pathways. We show that MaSC and MaTIC EMT programs induce primary cilia formation and Hedgehog (Hh) signaling, which has previously been implicated in both MaSC and MaTIC function. Moreover, ablation of these primary cilia is sufficient to repress Hh signaling, the stemness of MaSCs, and the tumor-forming potential of MaTICs. Together, our findings establish primary ciliogenesis and consequent Hh signaling as a key mechanism by which MaSC and MaTIC EMT programs promote stemness and thereby support mammary tissue outgrowth and tumors of basal origin. Keywords: EMT; primary cilia; hedgehog; stemness |
| first_indexed | 2024-09-23T15:01:26Z |
| format | Article |
| id | mit-1721.1/116331 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T15:01:26Z |
| publishDate | 2018 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/1163312022-10-02T00:02:38Z EMT programs promote basal mammary stem cell and tumor-initiating cell stemness by inducing primary ciliogenesis and Hedgehog signaling Kröger, Cornelia Ye, Xin Guen, Vincent Chavarria, Tony E Weinberg, Robert A Lees, Jacqueline Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Guen, Vincent Chavarria, Tony E Weinberg, Robert A Lees, Jacqueline Tissue regeneration relies on adult stem cells (SCs) that possess the ability to self-renew and produce differentiating progeny. In an analogous manner, the development of certain carcinomas depends on a small subset of tumor cells, called “tumor-initiating cells” (TICs), with SC-like properties. Mammary SCs (MaSCs) reside in the basal compartment of the mammary epithelium, and their neoplastic counterparts, mammary TICs (MaTICs), are thought to serve as the TICs for the claudin-low subtype of breast cancer. MaSCs and MaTICs both use epithelial–mesenchymal transition (EMT) programs to acquire SC properties, but the mechanism(s) connecting EMT programs to stemness remain unclear. Here we show that this depends on primary cilia, which are nonmotile, cell-surface structures that serve as platforms for receiving cues and enable activation of various signaling pathways. We show that MaSC and MaTIC EMT programs induce primary cilia formation and Hedgehog (Hh) signaling, which has previously been implicated in both MaSC and MaTIC function. Moreover, ablation of these primary cilia is sufficient to repress Hh signaling, the stemness of MaSCs, and the tumor-forming potential of MaTICs. Together, our findings establish primary ciliogenesis and consequent Hh signaling as a key mechanism by which MaSC and MaTIC EMT programs promote stemness and thereby support mammary tissue outgrowth and tumors of basal origin. Keywords: EMT; primary cilia; hedgehog; stemness 2018-06-15T14:30:05Z 2018-06-15T14:30:05Z 2017-11 2017-06 2018-06-13T16:10:21Z Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/116331 Guen, Vincent J. et al. “EMT Programs Promote Basal Mammary Stem Cell and Tumor-Initiating Cell Stemness by Inducing Primary Ciliogenesis and Hedgehog Signaling.” Proceedings of the National Academy of Sciences 114, 49 (November 2017): E10532–E10539 © 2017 National Academy of Sciences https://orcid.org/0000-0003-2175-4066 https://orcid.org/0000-0002-0895-3557 https://orcid.org/0000-0001-9451-2194 http://dx.doi.org/10.1073/PNAS.1711534114 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Kröger, Cornelia Ye, Xin Guen, Vincent Chavarria, Tony E Weinberg, Robert A Lees, Jacqueline EMT programs promote basal mammary stem cell and tumor-initiating cell stemness by inducing primary ciliogenesis and Hedgehog signaling |
| title | EMT programs promote basal mammary stem cell and tumor-initiating cell stemness by inducing primary ciliogenesis and Hedgehog signaling |
| title_full | EMT programs promote basal mammary stem cell and tumor-initiating cell stemness by inducing primary ciliogenesis and Hedgehog signaling |
| title_fullStr | EMT programs promote basal mammary stem cell and tumor-initiating cell stemness by inducing primary ciliogenesis and Hedgehog signaling |
| title_full_unstemmed | EMT programs promote basal mammary stem cell and tumor-initiating cell stemness by inducing primary ciliogenesis and Hedgehog signaling |
| title_short | EMT programs promote basal mammary stem cell and tumor-initiating cell stemness by inducing primary ciliogenesis and Hedgehog signaling |
| title_sort | emt programs promote basal mammary stem cell and tumor initiating cell stemness by inducing primary ciliogenesis and hedgehog signaling |
| url | http://hdl.handle.net/1721.1/116331 https://orcid.org/0000-0003-2175-4066 https://orcid.org/0000-0002-0895-3557 https://orcid.org/0000-0001-9451-2194 |
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