Targeting Taurine Transporter (TauT) for Cancer Immunotherapy of p53 Mutation Mediated Cancers – Molecular Basis and Preclinical Implication

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Taurine transporter (TauT) has been identified as a target gene of p53 tumor suppressor. TauT is also found to be overexpressed in variety type of human cancers, such as leukemia. This study showed that expression of TauT was upregulated by c-Myc and c-Jun oncogenes. To explore whether blocking of TauT inhibits tumor development, the RNA interference (RNAi) and immune targeting approaches were tested in tumor cells in vitro and in p53 mutant mice in vivo. Knockdown of TauT expression by RNAi resulted in cell cycle G2 arrest and suppressed human breast cancer MCF-7 cells proliferation determined by colonies production and cell migration assays. Knockdown of TauT also rendered MCF-7 cells more susceptible to chemotherapeutic drug-induced apoptosis. An antibody specifically against TauT blocked taurine uptake and induced cell cycle G2 arrest leading to cell death of variety type of tumor cells without affecting the viability of normal mammalian cells. TauT peptide vaccination significantly increased median lifespan (1.5-fold) of the p53 null mice and rescued p53+/− mice by extending the median lifespan from 315 days to 621 days. Furthermore, single dose treatment of tumor-bearing (thymic lymphoma) p53 null mice with TauT peptide reduced tumor size by about 50% and significantly prolonged survival of these mice from average 7 days (after observing the thymic lymphoma) to 21 days. This finding demonstrates that a novel TauT peptide vaccine can delay, inhibit, and/or treat p53 mutation related spontaneous tumorigenesis in vivo. Therefore, TauT peptide may be used as a universal cancer vaccine to prevent and/or treat patients with p53 mutation-mediated cancers.

Original languageEnglish (US)
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer New York LLC
Pages543-553
Number of pages11
DOIs
StatePublished - Jan 1 2019

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1155
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Fingerprint

Immunotherapy
Mutation
Tumors
Neoplasms
Cells
G2 Phase Cell Cycle Checkpoints
MCF-7 Cells
RNA Interference
Peptides
Lymphoma
taurine transporter
Bearings (structural)
Cell Migration Assays
jun Genes
RNA
Thymus Neoplasms
Cancer Vaccines
Subunit Vaccines
Taurine
Cell proliferation

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Han, X. (2019). Targeting Taurine Transporter (TauT) for Cancer Immunotherapy of p53 Mutation Mediated Cancers – Molecular Basis and Preclinical Implication. In Advances in Experimental Medicine and Biology (pp. 543-553). (Advances in Experimental Medicine and Biology; Vol. 1155). Springer New York LLC. https://doi.org/10.1007/978-981-13-8023-5_50

Targeting Taurine Transporter (TauT) for Cancer Immunotherapy of p53 Mutation Mediated Cancers – Molecular Basis and Preclinical Implication. / Han, Xiaobin.

Advances in Experimental Medicine and Biology. Springer New York LLC, 2019. p. 543-553 (Advances in Experimental Medicine and Biology; Vol. 1155).

Research output: Chapter in Book/Report/Conference proceedingChapter

Han, X 2019, Targeting Taurine Transporter (TauT) for Cancer Immunotherapy of p53 Mutation Mediated Cancers – Molecular Basis and Preclinical Implication. in Advances in Experimental Medicine and Biology. Advances in Experimental Medicine and Biology, vol. 1155, Springer New York LLC, pp. 543-553. https://doi.org/10.1007/978-981-13-8023-5_50
Han X. Targeting Taurine Transporter (TauT) for Cancer Immunotherapy of p53 Mutation Mediated Cancers – Molecular Basis and Preclinical Implication. In Advances in Experimental Medicine and Biology. Springer New York LLC. 2019. p. 543-553. (Advances in Experimental Medicine and Biology). https://doi.org/10.1007/978-981-13-8023-5_50
Han, Xiaobin. / Targeting Taurine Transporter (TauT) for Cancer Immunotherapy of p53 Mutation Mediated Cancers – Molecular Basis and Preclinical Implication. Advances in Experimental Medicine and Biology. Springer New York LLC, 2019. pp. 543-553 (Advances in Experimental Medicine and Biology).
@inbook{be35d8491d054dffb91c5625fb817a0c,
title = "Targeting Taurine Transporter (TauT) for Cancer Immunotherapy of p53 Mutation Mediated Cancers – Molecular Basis and Preclinical Implication",
abstract = "Taurine transporter (TauT) has been identified as a target gene of p53 tumor suppressor. TauT is also found to be overexpressed in variety type of human cancers, such as leukemia. This study showed that expression of TauT was upregulated by c-Myc and c-Jun oncogenes. To explore whether blocking of TauT inhibits tumor development, the RNA interference (RNAi) and immune targeting approaches were tested in tumor cells in vitro and in p53 mutant mice in vivo. Knockdown of TauT expression by RNAi resulted in cell cycle G2 arrest and suppressed human breast cancer MCF-7 cells proliferation determined by colonies production and cell migration assays. Knockdown of TauT also rendered MCF-7 cells more susceptible to chemotherapeutic drug-induced apoptosis. An antibody specifically against TauT blocked taurine uptake and induced cell cycle G2 arrest leading to cell death of variety type of tumor cells without affecting the viability of normal mammalian cells. TauT peptide vaccination significantly increased median lifespan (1.5-fold) of the p53 null mice and rescued p53+/− mice by extending the median lifespan from 315 days to 621 days. Furthermore, single dose treatment of tumor-bearing (thymic lymphoma) p53 null mice with TauT peptide reduced tumor size by about 50{\%} and significantly prolonged survival of these mice from average 7 days (after observing the thymic lymphoma) to 21 days. This finding demonstrates that a novel TauT peptide vaccine can delay, inhibit, and/or treat p53 mutation related spontaneous tumorigenesis in vivo. Therefore, TauT peptide may be used as a universal cancer vaccine to prevent and/or treat patients with p53 mutation-mediated cancers.",
author = "Xiaobin Han",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/978-981-13-8023-5_50",
language = "English (US)",
series = "Advances in Experimental Medicine and Biology",
publisher = "Springer New York LLC",
pages = "543--553",
booktitle = "Advances in Experimental Medicine and Biology",

}

TY - CHAP

T1 - Targeting Taurine Transporter (TauT) for Cancer Immunotherapy of p53 Mutation Mediated Cancers – Molecular Basis and Preclinical Implication

AU - Han, Xiaobin

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Taurine transporter (TauT) has been identified as a target gene of p53 tumor suppressor. TauT is also found to be overexpressed in variety type of human cancers, such as leukemia. This study showed that expression of TauT was upregulated by c-Myc and c-Jun oncogenes. To explore whether blocking of TauT inhibits tumor development, the RNA interference (RNAi) and immune targeting approaches were tested in tumor cells in vitro and in p53 mutant mice in vivo. Knockdown of TauT expression by RNAi resulted in cell cycle G2 arrest and suppressed human breast cancer MCF-7 cells proliferation determined by colonies production and cell migration assays. Knockdown of TauT also rendered MCF-7 cells more susceptible to chemotherapeutic drug-induced apoptosis. An antibody specifically against TauT blocked taurine uptake and induced cell cycle G2 arrest leading to cell death of variety type of tumor cells without affecting the viability of normal mammalian cells. TauT peptide vaccination significantly increased median lifespan (1.5-fold) of the p53 null mice and rescued p53+/− mice by extending the median lifespan from 315 days to 621 days. Furthermore, single dose treatment of tumor-bearing (thymic lymphoma) p53 null mice with TauT peptide reduced tumor size by about 50% and significantly prolonged survival of these mice from average 7 days (after observing the thymic lymphoma) to 21 days. This finding demonstrates that a novel TauT peptide vaccine can delay, inhibit, and/or treat p53 mutation related spontaneous tumorigenesis in vivo. Therefore, TauT peptide may be used as a universal cancer vaccine to prevent and/or treat patients with p53 mutation-mediated cancers.

AB - Taurine transporter (TauT) has been identified as a target gene of p53 tumor suppressor. TauT is also found to be overexpressed in variety type of human cancers, such as leukemia. This study showed that expression of TauT was upregulated by c-Myc and c-Jun oncogenes. To explore whether blocking of TauT inhibits tumor development, the RNA interference (RNAi) and immune targeting approaches were tested in tumor cells in vitro and in p53 mutant mice in vivo. Knockdown of TauT expression by RNAi resulted in cell cycle G2 arrest and suppressed human breast cancer MCF-7 cells proliferation determined by colonies production and cell migration assays. Knockdown of TauT also rendered MCF-7 cells more susceptible to chemotherapeutic drug-induced apoptosis. An antibody specifically against TauT blocked taurine uptake and induced cell cycle G2 arrest leading to cell death of variety type of tumor cells without affecting the viability of normal mammalian cells. TauT peptide vaccination significantly increased median lifespan (1.5-fold) of the p53 null mice and rescued p53+/− mice by extending the median lifespan from 315 days to 621 days. Furthermore, single dose treatment of tumor-bearing (thymic lymphoma) p53 null mice with TauT peptide reduced tumor size by about 50% and significantly prolonged survival of these mice from average 7 days (after observing the thymic lymphoma) to 21 days. This finding demonstrates that a novel TauT peptide vaccine can delay, inhibit, and/or treat p53 mutation related spontaneous tumorigenesis in vivo. Therefore, TauT peptide may be used as a universal cancer vaccine to prevent and/or treat patients with p53 mutation-mediated cancers.

UR - http://www.scopus.com/inward/record.url?scp=85071778742&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071778742&partnerID=8YFLogxK

U2 - 10.1007/978-981-13-8023-5_50

DO - 10.1007/978-981-13-8023-5_50

M3 - Chapter

C2 - 31468430

AN - SCOPUS:85071778742

T3 - Advances in Experimental Medicine and Biology

SP - 543

EP - 553

BT - Advances in Experimental Medicine and Biology

PB - Springer New York LLC

ER -