Nuclear translocation of PKM2/AMPK complex sustains cancer stem cell populations under glucose restriction stress

Yi Chieh Yang, Ming Hsien Chien, Hsin Yi Liu, Yu Chan Chang, Chi Kuan Chen, Wei Jiunn Lee, Tsang Chih Kuo, Michael Hsiao, Kuo Tai Hua, Tsu Yao Cheng

研究成果: 雜誌貢獻文章

7 引文 (Scopus)

摘要

Cancer cells encounter metabolic stresses such as hypoxia and nutrient limitations because they grow and divide more quickly than their normal counterparts. In response to glucose restriction, we found that nuclear translocation of the glycolic enzyme, pyruvate kinase M2 (PKM2), helped cancer cells survive under the metabolic stress. Restriction of glucose stimulated AMPK activation and resulted in co-translocation of AMPK and PKM2 through Ran-mediated nuclear transport. Nuclear PKM2 subsequently bound to Oct4 and promoted the expression of cancer stemness-related genes, which might enrich the cancer stem cell population under the metabolic stress. Nuclear PKM2 was also capable of promoting cancer metastasis in an orthotopic xenograft model. In summary, we found that cytosolic AMPK helped PKM2 carry out its nonmetabolic functions in the nucleus under glucose restriction and that nuclear PKM2 promoted cancer stemness and metastasis. These findings suggested a potential new targeting pathway for cancer therapy in the future.

原文英語
頁(從 - 到)28-40
頁數13
期刊Cancer Letters
421
DOIs
出版狀態已發佈 - 五月 1 2018

指紋

AMP-Activated Protein Kinases
Pyruvate Kinase
Neoplastic Stem Cells
Glucose
Physiological Stress
Population
Neoplasms
Neoplasm Metastasis
Cell Nucleus Active Transport
Heterografts
Food
Enzymes
Genes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

引用此文

Nuclear translocation of PKM2/AMPK complex sustains cancer stem cell populations under glucose restriction stress. / Yang, Yi Chieh; Chien, Ming Hsien; Liu, Hsin Yi; Chang, Yu Chan; Chen, Chi Kuan; Lee, Wei Jiunn; Kuo, Tsang Chih; Hsiao, Michael; Hua, Kuo Tai; Cheng, Tsu Yao.

於: Cancer Letters, 卷 421, 01.05.2018, p. 28-40.

研究成果: 雜誌貢獻文章

Yang, Yi Chieh ; Chien, Ming Hsien ; Liu, Hsin Yi ; Chang, Yu Chan ; Chen, Chi Kuan ; Lee, Wei Jiunn ; Kuo, Tsang Chih ; Hsiao, Michael ; Hua, Kuo Tai ; Cheng, Tsu Yao. / Nuclear translocation of PKM2/AMPK complex sustains cancer stem cell populations under glucose restriction stress. 於: Cancer Letters. 2018 ; 卷 421. 頁 28-40.
@article{bb78b51b75cd4c0a9ac9ec138c793e59,
title = "Nuclear translocation of PKM2/AMPK complex sustains cancer stem cell populations under glucose restriction stress",
abstract = "Cancer cells encounter metabolic stresses such as hypoxia and nutrient limitations because they grow and divide more quickly than their normal counterparts. In response to glucose restriction, we found that nuclear translocation of the glycolic enzyme, pyruvate kinase M2 (PKM2), helped cancer cells survive under the metabolic stress. Restriction of glucose stimulated AMPK activation and resulted in co-translocation of AMPK and PKM2 through Ran-mediated nuclear transport. Nuclear PKM2 subsequently bound to Oct4 and promoted the expression of cancer stemness-related genes, which might enrich the cancer stem cell population under the metabolic stress. Nuclear PKM2 was also capable of promoting cancer metastasis in an orthotopic xenograft model. In summary, we found that cytosolic AMPK helped PKM2 carry out its nonmetabolic functions in the nucleus under glucose restriction and that nuclear PKM2 promoted cancer stemness and metastasis. These findings suggested a potential new targeting pathway for cancer therapy in the future.",
keywords = "AMPK, Cancer stemness, Glucose restriction, Pyruvate kinase M2",
author = "Yang, {Yi Chieh} and Chien, {Ming Hsien} and Liu, {Hsin Yi} and Chang, {Yu Chan} and Chen, {Chi Kuan} and Lee, {Wei Jiunn} and Kuo, {Tsang Chih} and Michael Hsiao and Hua, {Kuo Tai} and Cheng, {Tsu Yao}",
year = "2018",
month = "5",
day = "1",
doi = "10.1016/j.canlet.2018.01.075",
language = "English",
volume = "421",
pages = "28--40",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Nuclear translocation of PKM2/AMPK complex sustains cancer stem cell populations under glucose restriction stress

AU - Yang, Yi Chieh

AU - Chien, Ming Hsien

AU - Liu, Hsin Yi

AU - Chang, Yu Chan

AU - Chen, Chi Kuan

AU - Lee, Wei Jiunn

AU - Kuo, Tsang Chih

AU - Hsiao, Michael

AU - Hua, Kuo Tai

AU - Cheng, Tsu Yao

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Cancer cells encounter metabolic stresses such as hypoxia and nutrient limitations because they grow and divide more quickly than their normal counterparts. In response to glucose restriction, we found that nuclear translocation of the glycolic enzyme, pyruvate kinase M2 (PKM2), helped cancer cells survive under the metabolic stress. Restriction of glucose stimulated AMPK activation and resulted in co-translocation of AMPK and PKM2 through Ran-mediated nuclear transport. Nuclear PKM2 subsequently bound to Oct4 and promoted the expression of cancer stemness-related genes, which might enrich the cancer stem cell population under the metabolic stress. Nuclear PKM2 was also capable of promoting cancer metastasis in an orthotopic xenograft model. In summary, we found that cytosolic AMPK helped PKM2 carry out its nonmetabolic functions in the nucleus under glucose restriction and that nuclear PKM2 promoted cancer stemness and metastasis. These findings suggested a potential new targeting pathway for cancer therapy in the future.

AB - Cancer cells encounter metabolic stresses such as hypoxia and nutrient limitations because they grow and divide more quickly than their normal counterparts. In response to glucose restriction, we found that nuclear translocation of the glycolic enzyme, pyruvate kinase M2 (PKM2), helped cancer cells survive under the metabolic stress. Restriction of glucose stimulated AMPK activation and resulted in co-translocation of AMPK and PKM2 through Ran-mediated nuclear transport. Nuclear PKM2 subsequently bound to Oct4 and promoted the expression of cancer stemness-related genes, which might enrich the cancer stem cell population under the metabolic stress. Nuclear PKM2 was also capable of promoting cancer metastasis in an orthotopic xenograft model. In summary, we found that cytosolic AMPK helped PKM2 carry out its nonmetabolic functions in the nucleus under glucose restriction and that nuclear PKM2 promoted cancer stemness and metastasis. These findings suggested a potential new targeting pathway for cancer therapy in the future.

KW - AMPK

KW - Cancer stemness

KW - Glucose restriction

KW - Pyruvate kinase M2

UR - http://www.scopus.com/inward/record.url?scp=85042234316&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042234316&partnerID=8YFLogxK

U2 - 10.1016/j.canlet.2018.01.075

DO - 10.1016/j.canlet.2018.01.075

M3 - Article

AN - SCOPUS:85042234316

VL - 421

SP - 28

EP - 40

JO - Cancer Letters

JF - Cancer Letters

SN - 0304-3835

ER -