Skip to main content
Erschienen in: Tumor Biology 3/2016

22.10.2015 | Original Article

PKM2 promotes stemness of breast cancer cell by through Wnt/β-catenin pathway

verfasst von: Zheng Zhao, Zhangjun Song, Zijun Liao, Zhigang Liu, Haifeng Sun, Baoxia Lei, Wenjuan Chen, Chengxue Dang

Erschienen in: Tumor Biology | Ausgabe 3/2016

Einloggen, um Zugang zu erhalten

Abstract

Metastasis is one of the main causes of breast cancer (BCa)-related deaths in female. It has been reported that cancer stem cell played an important role in metastasis. Here we first revealed a specific role of pyruvate kinase isozymes M2 (PKM2) in the stemness of breast cancer cells. Breast cancer tissue analysis confirmed the upregulation of PKM2 in breast cancer, and high PKM2 levels were associated with poor prognosis of breast cancer patients. Holoclone assay and colony formation assay significantly elucidated the role of PKM2 in the self-renewal of breast cancer cells. Moreover, PKM2 elevated the proportion of stem cell and the ability of sphere formation in breast cancer cells. PKM2 played its functional role in stemness by regulating β-catenin. Collectively, we identified critical roles of PKM2 in the stemness of breast cancer cells which may elevate the therapeutic effect on breast cancer patients.
Literatur
1.
Zurück zum Zitat Nemoto T, Vana J, Bedwani RN, Baker HW, McGregor FH, Murphy GP. Management and survival of female breast cancer: results of a national survey by the american college of surgeons. Cancer. 1980;45:2917–24.CrossRefPubMed Nemoto T, Vana J, Bedwani RN, Baker HW, McGregor FH, Murphy GP. Management and survival of female breast cancer: results of a national survey by the american college of surgeons. Cancer. 1980;45:2917–24.CrossRefPubMed
2.
Zurück zum Zitat Dings PJ, Elferink MA, Strobbe LJ, de Wilt JH. The prognostic value of lymph node ratio in node-positive breast cancer: a Dutch nationwide population-based study. Ann Surg Oncol. 2013;20:2607–14.CrossRefPubMed Dings PJ, Elferink MA, Strobbe LJ, de Wilt JH. The prognostic value of lymph node ratio in node-positive breast cancer: a Dutch nationwide population-based study. Ann Surg Oncol. 2013;20:2607–14.CrossRefPubMed
3.
Zurück zum Zitat Nawshad A, Lagamba D, Polad A, Hay ED. Transforming growth factor-beta signaling during epithelial-mesenchymal transformation: implications for embryogenesis and tumor metastasis. Cells Tissues Organs. 2005;179:11–23.CrossRefPubMed Nawshad A, Lagamba D, Polad A, Hay ED. Transforming growth factor-beta signaling during epithelial-mesenchymal transformation: implications for embryogenesis and tumor metastasis. Cells Tissues Organs. 2005;179:11–23.CrossRefPubMed
4.
Zurück zum Zitat Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3:730–7.CrossRefPubMed Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3:730–7.CrossRefPubMed
5.
Zurück zum Zitat Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, et al. Identification of pancreatic cancer stem cells. Cancer Res. 2007;67:1030–7.CrossRefPubMed Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, et al. Identification of pancreatic cancer stem cells. Cancer Res. 2007;67:1030–7.CrossRefPubMed
6.
Zurück zum Zitat Patrawala L, Calhoun T, Schneider-Broussard R, Li H, Bhatia B, Tang S, et al. Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene. 2006;25:1696–708.CrossRefPubMed Patrawala L, Calhoun T, Schneider-Broussard R, Li H, Bhatia B, Tang S, et al. Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene. 2006;25:1696–708.CrossRefPubMed
7.
Zurück zum Zitat Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003;63:5821–8.PubMed Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003;63:5821–8.PubMed
8.
Zurück zum Zitat Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, et al. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007;445:111–5.CrossRefPubMed Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, et al. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007;445:111–5.CrossRefPubMed
9.
Zurück zum Zitat Gupta PB, Chaffer CL, Weinberg RA. Cancer stem cells: mirage or reality? Nat Med. 2009;15:1010–2.CrossRefPubMed Gupta PB, Chaffer CL, Weinberg RA. Cancer stem cells: mirage or reality? Nat Med. 2009;15:1010–2.CrossRefPubMed
10.
Zurück zum Zitat Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414:105–11.CrossRefPubMed Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414:105–11.CrossRefPubMed
11.
Zurück zum Zitat Creighton CJ, Li X, Landis M, Dixon JM, Neumeister VM, Sjolund A, et al. Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc Natl Acad Sci U S A. 2009;106:13820–5.CrossRefPubMedPubMedCentral Creighton CJ, Li X, Landis M, Dixon JM, Neumeister VM, Sjolund A, et al. Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc Natl Acad Sci U S A. 2009;106:13820–5.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer. 2005;5:275–84.CrossRefPubMed Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer. 2005;5:275–84.CrossRefPubMed
13.
Zurück zum Zitat Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003;100:3983–8.CrossRefPubMedPubMedCentral Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003;100:3983–8.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Miki T, Yasuda SY, Kahn M. Wnt/beta-catenin signaling in embryonic stem cell self-renewal and somatic cell reprogramming. Stem Cell Rev. 2011;7:836–46.CrossRefPubMed Miki T, Yasuda SY, Kahn M. Wnt/beta-catenin signaling in embryonic stem cell self-renewal and somatic cell reprogramming. Stem Cell Rev. 2011;7:836–46.CrossRefPubMed
15.
Zurück zum Zitat Takahashi-Yanaga F, Kahn M. Targeting wnt signaling: can we safely eradicate cancer stem cells? Clin Cancer Res. 2010;16:3153–62.CrossRefPubMed Takahashi-Yanaga F, Kahn M. Targeting wnt signaling: can we safely eradicate cancer stem cells? Clin Cancer Res. 2010;16:3153–62.CrossRefPubMed
16.
Zurück zum Zitat Liu J, Sato C, Cerletti M, Wagers A. Notch signaling in the regulation of stem cell self-renewal and differentiation. Curr Top Dev Biol. 2010;92:367–409.CrossRefPubMed Liu J, Sato C, Cerletti M, Wagers A. Notch signaling in the regulation of stem cell self-renewal and differentiation. Curr Top Dev Biol. 2010;92:367–409.CrossRefPubMed
17.
Zurück zum Zitat Lin SY, Xia W, Wang JC, Kwong KY, Spohn B, Wen Y, et al. Beta-catenin, a novel prognostic marker for breast cancer: its roles in cyclin d1 expression and cancer progression. Proc Natl Acad Sci U S A. 2000;97:4262–6.CrossRefPubMedPubMedCentral Lin SY, Xia W, Wang JC, Kwong KY, Spohn B, Wen Y, et al. Beta-catenin, a novel prognostic marker for breast cancer: its roles in cyclin d1 expression and cancer progression. Proc Natl Acad Sci U S A. 2000;97:4262–6.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, et al. Identification of c-MYC as a target of the APC pathway. Science. 1998;281:1509–12.CrossRefPubMed He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, et al. Identification of c-MYC as a target of the APC pathway. Science. 1998;281:1509–12.CrossRefPubMed
19.
Zurück zum Zitat Kirstetter P, Anderson K, Porse BT, Jacobsen SE, Nerlov C. Activation of the canonical Wnt pathway leads to loss of hematopoietic stem cell repopulation and multilineage differentiation block. Nat Immunol. 2006;7:1048–56.CrossRefPubMed Kirstetter P, Anderson K, Porse BT, Jacobsen SE, Nerlov C. Activation of the canonical Wnt pathway leads to loss of hematopoietic stem cell repopulation and multilineage differentiation block. Nat Immunol. 2006;7:1048–56.CrossRefPubMed
20.
Zurück zum Zitat Yook JI, Li XY, Ota I, Hu C, Kim HS, Kim NH, et al. A Wnt-Axin2-GSK3beta cascade regulates Snail1 activity in breast cancer cells. Nat Cell Biol. 2006;8:1398–406.CrossRefPubMed Yook JI, Li XY, Ota I, Hu C, Kim HS, Kim NH, et al. A Wnt-Axin2-GSK3beta cascade regulates Snail1 activity in breast cancer cells. Nat Cell Biol. 2006;8:1398–406.CrossRefPubMed
21.
Zurück zum Zitat Tolle SW, Dyson RD, Newburgh RW, Cardenas JM. Pyruvate kinase isozymes in neurons, glia, neuroblastoma, and glioblastoma. J Neurochem. 1976;27:1355–60.CrossRefPubMed Tolle SW, Dyson RD, Newburgh RW, Cardenas JM. Pyruvate kinase isozymes in neurons, glia, neuroblastoma, and glioblastoma. J Neurochem. 1976;27:1355–60.CrossRefPubMed
22.
Zurück zum Zitat Brinck U, Eigenbrodt E, Oehmke M, Mazurek S, Fischer G. L- and m2-pyruvate kinase expression in renal cell carcinomas and their metastases. Virchows Arch. 1994;424:177–85.CrossRefPubMed Brinck U, Eigenbrodt E, Oehmke M, Mazurek S, Fischer G. L- and m2-pyruvate kinase expression in renal cell carcinomas and their metastases. Virchows Arch. 1994;424:177–85.CrossRefPubMed
25.
Zurück zum Zitat Moon RT. Wnt/beta-catenin pathway. Sci STKE. 2005;2005. Moon RT. Wnt/beta-catenin pathway. Sci STKE. 2005;2005.
26.
Zurück zum Zitat Teo JL, Kahn M. The Wnt signaling pathway in cellular proliferation and differentiation: a tale of two coactivators. Adv Drug Deliv Rev. 2010;62:1149–55.CrossRefPubMed Teo JL, Kahn M. The Wnt signaling pathway in cellular proliferation and differentiation: a tale of two coactivators. Adv Drug Deliv Rev. 2010;62:1149–55.CrossRefPubMed
27.
28.
Zurück zum Zitat Jamieson CH, Weissman IL, Passegue E. Chronic versus acute myelogenous leukemia: a question of self-renewal. Cancer Cell. 2004;6:531–3.PubMed Jamieson CH, Weissman IL, Passegue E. Chronic versus acute myelogenous leukemia: a question of self-renewal. Cancer Cell. 2004;6:531–3.PubMed
29.
Zurück zum Zitat Armanios M, Greider CW. Telomerase and cancer stem cells. Cold Spring Harb Symp Quant Biol. 2005;70:205–8.CrossRefPubMed Armanios M, Greider CW. Telomerase and cancer stem cells. Cold Spring Harb Symp Quant Biol. 2005;70:205–8.CrossRefPubMed
30.
Zurück zum Zitat Hussenet T, Dembele D, Martinet N, Vignaud JM, du Manoir S. An adult tissue-specific stem cell molecular phenotype is activated in epithelial cancer stem cells and correlated to patient outcome. Cell Cycle. 2010;9:321–7.CrossRefPubMed Hussenet T, Dembele D, Martinet N, Vignaud JM, du Manoir S. An adult tissue-specific stem cell molecular phenotype is activated in epithelial cancer stem cells and correlated to patient outcome. Cell Cycle. 2010;9:321–7.CrossRefPubMed
32.
Zurück zum Zitat Parmar A, Marz S, Rushton S, Holzwarth C, Lind K, Kayser S, et al. Stromal niche cells protect early leukemic FLT3-ITD+progenitor cells against first-generation FLT3 tyrosine kinase inhibitors. Cancer Res. 2011;71:4696–706.CrossRefPubMed Parmar A, Marz S, Rushton S, Holzwarth C, Lind K, Kayser S, et al. Stromal niche cells protect early leukemic FLT3-ITD+progenitor cells against first-generation FLT3 tyrosine kinase inhibitors. Cancer Res. 2011;71:4696–706.CrossRefPubMed
33.
Zurück zum Zitat Lang J, Lan X, Liu Y, Jin X, Wu T, Sun X, et al. Targeting cancer stem cells with an 131i-labeled anti-AC133 monoclonal antibody in human colorectal cancer xenografts. Nucl Med Biol. 2015;42:505–12.CrossRefPubMed Lang J, Lan X, Liu Y, Jin X, Wu T, Sun X, et al. Targeting cancer stem cells with an 131i-labeled anti-AC133 monoclonal antibody in human colorectal cancer xenografts. Nucl Med Biol. 2015;42:505–12.CrossRefPubMed
34.
Zurück zum Zitat Barrandon Y, Green H. Three clonal types of keratinocyte with different capacities for multiplication. Proc Natl Acad Sci U S A. 1987;84:2302–6.CrossRefPubMedPubMedCentral Barrandon Y, Green H. Three clonal types of keratinocyte with different capacities for multiplication. Proc Natl Acad Sci U S A. 1987;84:2302–6.CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Ang YS, Tsai SY, Lee DF, Monk J, Su J, Ratnakumar K, et al. Wdr5 mediates self-renewal and reprogramming via the embryonic stem cell core transcriptional network. Cell. 2011;145:183–97.CrossRefPubMedPubMedCentral Ang YS, Tsai SY, Lee DF, Monk J, Su J, Ratnakumar K, et al. Wdr5 mediates self-renewal and reprogramming via the embryonic stem cell core transcriptional network. Cell. 2011;145:183–97.CrossRefPubMedPubMedCentral
Metadaten
Titel
PKM2 promotes stemness of breast cancer cell by through Wnt/β-catenin pathway
verfasst von
Zheng Zhao
Zhangjun Song
Zijun Liao
Zhigang Liu
Haifeng Sun
Baoxia Lei
Wenjuan Chen
Chengxue Dang
Publikationsdatum
22.10.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 3/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4121-8

Weitere Artikel der Ausgabe 3/2016

Tumor Biology 3/2016 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.