GLO 1 and PKCλ regulate ALDH1-positive breast cancer stem cell survival

Hitomi Motomura; Shoma Tamori; Masa Aki Yatani; Ayano Namiki; Chotaro Onaga; Ayaka Ozaki; Ryoko Takasawa; Yasunari Mano; Tsugumichi Sato; Yasushi Hara; Keiko Sato; Yuyun Xiong; Yohsuke Harada; Takehisa Hanawa; Sei Ichi Tanuma; Kazunori Sasaki; Shigeo Ohno; Kazunori Akimoto

doi:10.21873/anticanres.15415

GLO 1 and PKCλ regulate ALDH1-positive breast cancer stem cell survival

Hitomi Motomura, Shoma Tamori, Masa Aki Yatani, Ayano Namiki, Chotaro Onaga, Ayaka Ozaki, Ryoko Takasawa, Yasunari Mano, Tsugumichi Sato, Yasushi Hara, Keiko Sato, Yuyun Xiong, Yohsuke Harada, Takehisa Hanawa, Sei Ichi Tanuma, Kazunori Sasaki, Shigeo Ohno, Kazunori Akimoto

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

Abstract

Background/Aim: We examined the inhibitory effects of both glyoxalase 1 (GLO 1) and protein kinase C (PKC)λ in aldehyde dehydrogenase 1 (ALDH1)-positive breast cancer stem cells (CSCs). Materials and Methods: Breast cancer genomics datasets (TCGA, n=593; METABRIC, n=1904) were downloaded and statistically analyzed. The effects of GLO 1 and PKCλ on trypan blue staining and tumor-sphere formation by ALDH1^high cells derived from triple negative breast cancer (TNBC) and basal-like breast cancer were examined. Results: GLO 1^high, PKCλ^high, and ALDH1A3^high tumors were enriched in stage I/II/III/IV samples, associated with the HER2 and TNBC subtypes according to receptor status, and associated with the HER2-enriched and basal-like subtypes according to PAM50. Inhibition of either GLO 1 (TLSC702) or PKCλ (ANF) suppressed tumor-sphere formation and enhanced death in ALDH1^high cells. TLSC702 also effectively inhibited tumor-sphere formation and induced death in PKCλ knockout ALDH1^high cells. Conclusion: GLO 1 and PKCλ are important for the survival of ALDH1-positive breast CSCs, and may represent potential therapeutic targets for the treatment of ALDH1-positive breast CSCs.

Original language	English
Pages (from-to)	5959-5971
Number of pages	13
Journal	Anticancer research
Volume	41
Issue number	12
DOIs	https://doi.org/10.21873/anticanres.15415
Publication status	Published - Dec 2021

Keywords

ALDH1A3
Breast cancer
Cancer stem cell
GLO 1
PKCλ

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10.21873/anticanres.15415

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Motomura, H., Tamori, S., Yatani, M. A., Namiki, A., Onaga, C., Ozaki, A., Takasawa, R., Mano, Y., Sato, T., Hara, Y., Sato, K., Xiong, Y., Harada, Y., Hanawa, T., Tanuma, S. I., Sasaki, K., Ohno, S., & Akimoto, K. (2021). GLO 1 and PKCλ regulate ALDH1-positive breast cancer stem cell survival. Anticancer research, 41(12), 5959-5971. https://doi.org/10.21873/anticanres.15415

Motomura, Hitomi ; Tamori, Shoma ; Yatani, Masa Aki ; Namiki, Ayano ; Onaga, Chotaro ; Ozaki, Ayaka ; Takasawa, Ryoko ; Mano, Yasunari ; Sato, Tsugumichi ; Hara, Yasushi ; Sato, Keiko ; Xiong, Yuyun ; Harada, Yohsuke ; Hanawa, Takehisa ; Tanuma, Sei Ichi ; Sasaki, Kazunori ; Ohno, Shigeo ; Akimoto, Kazunori. / GLO 1 and PKCλ regulate ALDH1-positive breast cancer stem cell survival. In: Anticancer research. 2021 ; Vol. 41, No. 12. pp. 5959-5971.

@article{a183576dd7ab4dad98563d7b613bb1b6,

title = "GLO 1 and PKCλ regulate ALDH1-positive breast cancer stem cell survival",

abstract = "Background/Aim: We examined the inhibitory effects of both glyoxalase 1 (GLO 1) and protein kinase C (PKC)λ in aldehyde dehydrogenase 1 (ALDH1)-positive breast cancer stem cells (CSCs). Materials and Methods: Breast cancer genomics datasets (TCGA, n=593; METABRIC, n=1904) were downloaded and statistically analyzed. The effects of GLO 1 and PKCλ on trypan blue staining and tumor-sphere formation by ALDH1high cells derived from triple negative breast cancer (TNBC) and basal-like breast cancer were examined. Results: GLO 1high, PKCλhigh, and ALDH1A3high tumors were enriched in stage I/II/III/IV samples, associated with the HER2 and TNBC subtypes according to receptor status, and associated with the HER2-enriched and basal-like subtypes according to PAM50. Inhibition of either GLO 1 (TLSC702) or PKCλ (ANF) suppressed tumor-sphere formation and enhanced death in ALDH1high cells. TLSC702 also effectively inhibited tumor-sphere formation and induced death in PKCλ knockout ALDH1high cells. Conclusion: GLO 1 and PKCλ are important for the survival of ALDH1-positive breast CSCs, and may represent potential therapeutic targets for the treatment of ALDH1-positive breast CSCs.",

keywords = "ALDH1A3, Breast cancer, Cancer stem cell, GLO 1, PKCλ",

author = "Hitomi Motomura and Shoma Tamori and Yatani, {Masa Aki} and Ayano Namiki and Chotaro Onaga and Ayaka Ozaki and Ryoko Takasawa and Yasunari Mano and Tsugumichi Sato and Yasushi Hara and Keiko Sato and Yuyun Xiong and Yohsuke Harada and Takehisa Hanawa and Tanuma, {Sei Ichi} and Kazunori Sasaki and Shigeo Ohno and Kazunori Akimoto",

note = "Funding Information: The research was supported by Grant-in-Aid for Scientific Research (C) of JSPS, Tokyo, Japan (20K07207) (K.A.), JST Moonshot R&D, Saitama, Japan (JPMJPS2022) (S.O.), Grant-in-Aid for JSPS Research Fellows, Tokyo, Japan (21J13718) (H.M.) and (20J11980) (S.T.), Grant-in-Aid for Research Activity Start-up, Tokyo, Japan (21K20732) (S.T.), and Nagai Memorial Research Scholarship from the Pharmaceutical Society of Japan, Tokyo, Japan (H.M. and A.O.). Publisher Copyright: {\textcopyright} 2021 International Institute of Anticancer Research. All rights reserved.",

year = "2021",

month = dec,

doi = "10.21873/anticanres.15415",

language = "English",

volume = "41",

pages = "5959--5971",

journal = "Anticancer Research",

issn = "0250-7005",

publisher = "International Institute of Anticancer Research",

number = "12",

}

GLO 1 and PKCλ regulate ALDH1-positive breast cancer stem cell survival. / Motomura, Hitomi; Tamori, Shoma; Yatani, Masa Aki; Namiki, Ayano; Onaga, Chotaro; Ozaki, Ayaka; Takasawa, Ryoko ; Mano, Yasunari ; Sato, Tsugumichi; Hara, Yasushi; Sato, Keiko; Xiong, Yuyun; Harada, Yohsuke ; Hanawa, Takehisa; Tanuma, Sei Ichi; Sasaki, Kazunori; Ohno, Shigeo; Akimoto, Kazunori.

In: Anticancer research, Vol. 41, No. 12, 12.2021, p. 5959-5971.

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

TY - JOUR

T1 - GLO 1 and PKCλ regulate ALDH1-positive breast cancer stem cell survival

AU - Motomura, Hitomi

AU - Tamori, Shoma

AU - Yatani, Masa Aki

AU - Namiki, Ayano

AU - Onaga, Chotaro

AU - Ozaki, Ayaka

AU - Takasawa, Ryoko

AU - Mano, Yasunari

AU - Sato, Tsugumichi

AU - Hara, Yasushi

AU - Sato, Keiko

AU - Xiong, Yuyun

AU - Harada, Yohsuke

AU - Hanawa, Takehisa

AU - Tanuma, Sei Ichi

AU - Sasaki, Kazunori

AU - Ohno, Shigeo

AU - Akimoto, Kazunori

N1 - Funding Information: The research was supported by Grant-in-Aid for Scientific Research (C) of JSPS, Tokyo, Japan (20K07207) (K.A.), JST Moonshot R&D, Saitama, Japan (JPMJPS2022) (S.O.), Grant-in-Aid for JSPS Research Fellows, Tokyo, Japan (21J13718) (H.M.) and (20J11980) (S.T.), Grant-in-Aid for Research Activity Start-up, Tokyo, Japan (21K20732) (S.T.), and Nagai Memorial Research Scholarship from the Pharmaceutical Society of Japan, Tokyo, Japan (H.M. and A.O.). Publisher Copyright: © 2021 International Institute of Anticancer Research. All rights reserved.

PY - 2021/12

Y1 - 2021/12

N2 - Background/Aim: We examined the inhibitory effects of both glyoxalase 1 (GLO 1) and protein kinase C (PKC)λ in aldehyde dehydrogenase 1 (ALDH1)-positive breast cancer stem cells (CSCs). Materials and Methods: Breast cancer genomics datasets (TCGA, n=593; METABRIC, n=1904) were downloaded and statistically analyzed. The effects of GLO 1 and PKCλ on trypan blue staining and tumor-sphere formation by ALDH1high cells derived from triple negative breast cancer (TNBC) and basal-like breast cancer were examined. Results: GLO 1high, PKCλhigh, and ALDH1A3high tumors were enriched in stage I/II/III/IV samples, associated with the HER2 and TNBC subtypes according to receptor status, and associated with the HER2-enriched and basal-like subtypes according to PAM50. Inhibition of either GLO 1 (TLSC702) or PKCλ (ANF) suppressed tumor-sphere formation and enhanced death in ALDH1high cells. TLSC702 also effectively inhibited tumor-sphere formation and induced death in PKCλ knockout ALDH1high cells. Conclusion: GLO 1 and PKCλ are important for the survival of ALDH1-positive breast CSCs, and may represent potential therapeutic targets for the treatment of ALDH1-positive breast CSCs.

AB - Background/Aim: We examined the inhibitory effects of both glyoxalase 1 (GLO 1) and protein kinase C (PKC)λ in aldehyde dehydrogenase 1 (ALDH1)-positive breast cancer stem cells (CSCs). Materials and Methods: Breast cancer genomics datasets (TCGA, n=593; METABRIC, n=1904) were downloaded and statistically analyzed. The effects of GLO 1 and PKCλ on trypan blue staining and tumor-sphere formation by ALDH1high cells derived from triple negative breast cancer (TNBC) and basal-like breast cancer were examined. Results: GLO 1high, PKCλhigh, and ALDH1A3high tumors were enriched in stage I/II/III/IV samples, associated with the HER2 and TNBC subtypes according to receptor status, and associated with the HER2-enriched and basal-like subtypes according to PAM50. Inhibition of either GLO 1 (TLSC702) or PKCλ (ANF) suppressed tumor-sphere formation and enhanced death in ALDH1high cells. TLSC702 also effectively inhibited tumor-sphere formation and induced death in PKCλ knockout ALDH1high cells. Conclusion: GLO 1 and PKCλ are important for the survival of ALDH1-positive breast CSCs, and may represent potential therapeutic targets for the treatment of ALDH1-positive breast CSCs.

KW - ALDH1A3

KW - Breast cancer

KW - Cancer stem cell

KW - GLO 1

KW - PKCλ

UR - http://www.scopus.com/inward/record.url?scp=85120476069&partnerID=8YFLogxK

U2 - 10.21873/anticanres.15415

DO - 10.21873/anticanres.15415

M3 - Article

C2 - 34848450

AN - SCOPUS:85120476069

VL - 41

SP - 5959

EP - 5971

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 12

ER -

GLO 1 and PKCλ regulate ALDH1-positive breast cancer stem cell survival

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