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 Setlik & 10 others Michael 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

Research output: Contribution to journalArticle

110 Citations (Scopus)

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.

LanguageEnglish
Pages800-814
Number of pages15
JournalCancer Cell
Volume28
Issue number6
DOIs
Publication statusPublished - 14 Dec 2015

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

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. In: Cancer Cell. 2015 ; Vol. 28, No. 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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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, vol. 28, no. 6, pp. 800-814. https://doi.org/10.1016/j.ccell.2015.10.003

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.

In: Cancer Cell, Vol. 28, No. 6, 14.12.2015, p. 800-814.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mist1 Expressing Gastric Stem Cells Maintain the Normal and Neoplastic Gastric Epithelium and Are Supported by a Perivascular Stem Cell Niche

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

Y1 - 2015/12/14

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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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U2 - 10.1016/j.ccell.2015.10.003

DO - 10.1016/j.ccell.2015.10.003

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SP - 800

EP - 814

JO - Cancer Cell

T2 - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

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