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; 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

doi: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

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

Research output: Contribution to journal › Article › peer-review

247 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.

Original language	English
Pages (from-to)	800-814
Number of pages	15
Journal	Cancer Cell
Volume	28
Issue number	6
DOIs	https://doi.org/10.1016/j.ccell.2015.10.003
Publication status	Published or Issued - 14 Dec 2015
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.ccell.2015.10.003

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Hayakawa, Y., Ariyama, H., Stancikova, J., Sakitani, K., Asfaha, S., Renz, B. W., Dubeykovskaya, Z. A., Shibata, W., Wang, H., Westphalen, C. B., Chen, X., Takemoto, Y., Kim, W., Khurana, S. S., Tailor, Y., Nagar, K., Tomita, H., Hara, A., Sepulveda, A. R., ... Wang, T. C. (2015). Mist1 Expressing Gastric Stem Cells Maintain the Normal and Neoplastic Gastric Epithelium and Are Supported by a Perivascular Stem Cell Niche. Cancer Cell, 28(6), 800-814. https://doi.org/10.1016/j.ccell.2015.10.003

@article{cf477c1e6d2d4769ad793a049950c704,

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

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.}",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

month = dec,

day = "14",

doi = "10.1016/j.ccell.2015.10.003",

language = "English",

volume = "28",

pages = "800--814",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "6",

}

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

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

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.

UR - http://www.scopus.com/inward/record.url?scp=84954214835&partnerID=8YFLogxK

U2 - 10.1016/j.ccell.2015.10.003

DO - 10.1016/j.ccell.2015.10.003

M3 - Article

C2 - 26585400

AN - SCOPUS:84954214835

SN - 1535-6108

VL - 28

SP - 800

EP - 814

JO - Cancer Cell

JF - Cancer Cell

IS - 6

ER -

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

Abstract

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