Mist1 Expressing Gastric Stem Cells Maintain the Normal and Neoplastic Gastric Epithelium and Are Supported by a Perivascular Stem Cell Niche

Yoku Hayakawa, Hiroshi Ariyama, Jitka Stancikova, Kosuke Sakitani, Samuel Asfaha, Bernhard W. Renz, Zinaida A. Dubeykovskaya, Wataru Shibata, Hongshan Wang, Christoph B. Westphalen, Xiaowei Chen, Yoshihiro Takemoto, Woosook Kim, Shradha S. Khurana, Yagnesh Tailor, Karan Nagar, Hiroyuki Tomita, Akira Hara, Antonia R. Sepulveda, Wanda SetlikMichael D. Gershon, Subhrajit Saha, Lei Ding, Zeli Shen, James G. Fox, Richard A. Friedman, Stephen F. Konieczny, Daniel L. Worthley, Vladimir Korinek, Timothy C. Wang

    研究成果: ジャーナルへの寄稿記事

    110 引用 (Scopus)

    抄録

    The regulation and stem cell origin of normal and neoplastic gastric glands are uncertain. Here, we show that Mist1 expression marks quiescent stem cells in the gastric corpus isthmus. Mist1+ stem cells serve as a cell-of-origin for intestinal-type cancer with the combination of Kras and Apc mutation and for diffuse-type cancer with the loss of E-cadherin. Diffuse-type cancer development is dependent on inflammation mediated by Cxcl12+ endothelial cells and Cxcr4+ gastric innate lymphoid cells (ILCs). These cells form the perivascular gastric stem cell niche, and Wnt5a produced from ILCs activates RhoA to inhibit anoikis in the E-cadherin-depleted cells. Targeting Cxcr4, ILCs, or Wnt5a inhibits diffuse-type gastric carcinogenesis, providing targets within the neoplastic gastric stem cell niche.

    元の言語英語
    ページ(範囲)800-814
    ページ数15
    ジャーナルCancer Cell
    28
    発行部数6
    DOI
    出版物ステータス出版済み - 12 14 2015

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    Stem Cell Niche
    Stomach
    Stem Cells
    Epithelium
    Lymphocytes
    Cadherins
    Anoikis
    Intestinal Neoplasms
    Neoplastic Stem Cells
    Gastric Mucosa
    Neoplasms
    Carcinogenesis
    Endothelial Cells
    Inflammation
    Mutation

    All Science Journal Classification (ASJC) codes

    • Oncology
    • Cell Biology
    • Cancer Research

    これを引用

    Mist1 Expressing Gastric Stem Cells Maintain the Normal and Neoplastic Gastric Epithelium and Are Supported by a Perivascular Stem Cell Niche. / Hayakawa, Yoku; Ariyama, Hiroshi; Stancikova, Jitka; Sakitani, Kosuke; Asfaha, Samuel; Renz, Bernhard W.; Dubeykovskaya, Zinaida A.; Shibata, Wataru; Wang, Hongshan; Westphalen, Christoph B.; Chen, Xiaowei; Takemoto, Yoshihiro; Kim, Woosook; Khurana, Shradha S.; Tailor, Yagnesh; Nagar, Karan; Tomita, Hiroyuki; Hara, Akira; Sepulveda, Antonia R.; Setlik, Wanda; Gershon, Michael D.; Saha, Subhrajit; Ding, Lei; Shen, Zeli; Fox, James G.; Friedman, Richard A.; Konieczny, Stephen F.; Worthley, Daniel L.; Korinek, Vladimir; Wang, Timothy C.

    :: Cancer Cell, 巻 28, 番号 6, 14.12.2015, p. 800-814.

    研究成果: ジャーナルへの寄稿記事

    Hayakawa, Y, Ariyama, H, Stancikova, J, Sakitani, K, Asfaha, S, Renz, BW, Dubeykovskaya, ZA, Shibata, W, Wang, H, Westphalen, CB, Chen, X, Takemoto, Y, Kim, W, Khurana, SS, Tailor, Y, Nagar, K, Tomita, H, Hara, A, Sepulveda, AR, Setlik, W, Gershon, MD, Saha, S, Ding, L, Shen, Z, Fox, JG, Friedman, RA, Konieczny, SF, Worthley, DL, Korinek, V & Wang, TC 2015, 'Mist1 Expressing Gastric Stem Cells Maintain the Normal and Neoplastic Gastric Epithelium and Are Supported by a Perivascular Stem Cell Niche', Cancer Cell, 巻. 28, 番号 6, pp. 800-814. https://doi.org/10.1016/j.ccell.2015.10.003
    Hayakawa, Yoku ; Ariyama, Hiroshi ; Stancikova, Jitka ; Sakitani, Kosuke ; Asfaha, Samuel ; Renz, Bernhard W. ; Dubeykovskaya, Zinaida A. ; Shibata, Wataru ; Wang, Hongshan ; Westphalen, Christoph B. ; Chen, Xiaowei ; Takemoto, Yoshihiro ; Kim, Woosook ; Khurana, Shradha S. ; Tailor, Yagnesh ; Nagar, Karan ; Tomita, Hiroyuki ; Hara, Akira ; Sepulveda, Antonia R. ; Setlik, Wanda ; Gershon, Michael D. ; Saha, Subhrajit ; Ding, Lei ; Shen, Zeli ; Fox, James G. ; Friedman, Richard A. ; Konieczny, Stephen F. ; Worthley, Daniel L. ; Korinek, Vladimir ; Wang, Timothy C. / Mist1 Expressing Gastric Stem Cells Maintain the Normal and Neoplastic Gastric Epithelium and Are Supported by a Perivascular Stem Cell Niche. :: Cancer Cell. 2015 ; 巻 28, 番号 6. pp. 800-814.
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    abstract = "The regulation and stem cell origin of normal and neoplastic gastric glands are uncertain. Here, we show that Mist1 expression marks quiescent stem cells in the gastric corpus isthmus. Mist1+ stem cells serve as a cell-of-origin for intestinal-type cancer with the combination of Kras and Apc mutation and for diffuse-type cancer with the loss of E-cadherin. Diffuse-type cancer development is dependent on inflammation mediated by Cxcl12+ endothelial cells and Cxcr4+ gastric innate lymphoid cells (ILCs). These cells form the perivascular gastric stem cell niche, and Wnt5a produced from ILCs activates RhoA to inhibit anoikis in the E-cadherin-depleted cells. Targeting Cxcr4, ILCs, or Wnt5a inhibits diffuse-type gastric carcinogenesis, providing targets within the neoplastic gastric stem cell niche.",
    author = "Yoku Hayakawa and Hiroshi Ariyama and Jitka Stancikova and Kosuke Sakitani and Samuel Asfaha and Renz, {Bernhard W.} and Dubeykovskaya, {Zinaida A.} and Wataru Shibata and Hongshan Wang and Westphalen, {Christoph B.} and Xiaowei Chen and Yoshihiro Takemoto and Woosook Kim and Khurana, {Shradha S.} and Yagnesh Tailor and Karan Nagar and Hiroyuki Tomita and Akira Hara and Sepulveda, {Antonia R.} and Wanda Setlik and Gershon, {Michael D.} and Subhrajit Saha and Lei Ding and Zeli Shen and Fox, {James G.} and Friedman, {Richard A.} and Konieczny, {Stephen F.} and Worthley, {Daniel L.} and Vladimir Korinek and Wang, {Timothy C.}",
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    AU - Hayakawa, Yoku

    AU - Ariyama, Hiroshi

    AU - Stancikova, Jitka

    AU - Sakitani, Kosuke

    AU - Asfaha, Samuel

    AU - Renz, Bernhard W.

    AU - Dubeykovskaya, Zinaida A.

    AU - Shibata, Wataru

    AU - Wang, Hongshan

    AU - Westphalen, Christoph B.

    AU - Chen, Xiaowei

    AU - Takemoto, Yoshihiro

    AU - Kim, Woosook

    AU - Khurana, Shradha S.

    AU - Tailor, Yagnesh

    AU - Nagar, Karan

    AU - Tomita, Hiroyuki

    AU - Hara, Akira

    AU - Sepulveda, Antonia R.

    AU - Setlik, Wanda

    AU - Gershon, Michael D.

    AU - Saha, Subhrajit

    AU - Ding, Lei

    AU - Shen, Zeli

    AU - Fox, James G.

    AU - Friedman, Richard A.

    AU - Konieczny, Stephen F.

    AU - Worthley, Daniel L.

    AU - Korinek, Vladimir

    AU - Wang, Timothy C.

    PY - 2015/12/14

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    N2 - The regulation and stem cell origin of normal and neoplastic gastric glands are uncertain. Here, we show that Mist1 expression marks quiescent stem cells in the gastric corpus isthmus. Mist1+ stem cells serve as a cell-of-origin for intestinal-type cancer with the combination of Kras and Apc mutation and for diffuse-type cancer with the loss of E-cadherin. Diffuse-type cancer development is dependent on inflammation mediated by Cxcl12+ endothelial cells and Cxcr4+ gastric innate lymphoid cells (ILCs). These cells form the perivascular gastric stem cell niche, and Wnt5a produced from ILCs activates RhoA to inhibit anoikis in the E-cadherin-depleted cells. Targeting Cxcr4, ILCs, or Wnt5a inhibits diffuse-type gastric carcinogenesis, providing targets within the neoplastic gastric stem cell niche.

    AB - The regulation and stem cell origin of normal and neoplastic gastric glands are uncertain. Here, we show that Mist1 expression marks quiescent stem cells in the gastric corpus isthmus. Mist1+ stem cells serve as a cell-of-origin for intestinal-type cancer with the combination of Kras and Apc mutation and for diffuse-type cancer with the loss of E-cadherin. Diffuse-type cancer development is dependent on inflammation mediated by Cxcl12+ endothelial cells and Cxcr4+ gastric innate lymphoid cells (ILCs). These cells form the perivascular gastric stem cell niche, and Wnt5a produced from ILCs activates RhoA to inhibit anoikis in the E-cadherin-depleted cells. Targeting Cxcr4, ILCs, or Wnt5a inhibits diffuse-type gastric carcinogenesis, providing targets within the neoplastic gastric stem cell niche.

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