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Role of TCTP for Cellular Differentiation and Cancer Therapy

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Book cover TCTP/tpt1 - Remodeling Signaling from Stem Cell to Disease

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 64))

Abstract

The translationally controlled tumor protein (TCTP) is a highly conserved protein that is regulated due to a high number of extracellular stimuli. TCTP has an important role for cell cycle and normal development. On the other side, tumor reversion and malignant transformation have been associated with TCTP. TCTP has been found among the 12 genes that are differentially expressed during mouse oocyte maturation, and an overexpression of this gene was reported in a wide variety of different cancer types. Its antiapoptotic effect is indicated by the interaction with several proapoptotic proteins of the Bcl-2 family and the p53 tumor suppressor protein. In this article, we draw attention to the role of TCTP in cancer, especially, focusing on cell differentiation and tumor reversion, a biological process by which highly tumorigenic cells lose their malignant phenotype. This protein has been shown to be the most strongly downregulated protein in revertant cells compared to the parental cancer cells. Decreased expression of TCTP results either in the reprogramming of cancer cells into reversion or apoptosis. As conventional chemotherapy is frequently associated with the development of drug resistance and high toxicity, the urge for the development of new or additional scientific approaches falls into place. Differentiation therapy aims at reinducing differentiation backward to the nonmalignant cellular state. Here, different approaches have been reported such as the induction of retinoid pathways and the use of histone deacetylase inhibitors. Also, PPARγ agonists and the activation of the vitamin D receptor have been reported as potential targets in differentiation therapy. As TCTP is known as the histamine-releasing factor, antihistaminic drugs have been shown to target this protein. Antihistaminic compounds, hydroxyzine and promethazine, inhibited cell growth of cancer cells and decreased TCTP expression of breast cancer and leukemia cells. Recently, we found that two antihistaminics, levomepromazine and buclizine, inhibited cancer cell growth by direct binding to TCTP and induction of cell differentiation. These data confirmed that TCTP is an exquisite target for anticancer differentiation therapy and antihistaminics have potential to be lead compounds for the direct interaction with TCTP as new inhibitors of human TCTP and tumor growth.

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Abbreviations

ADDS:

Adenylosuccinate synthase

AIF:

Apoptosis-inducing factor

APL:

Acute promyelocytic leukemia

ATRA:

All-trans retinoic acid

Bcl-2:

B-cell lymphoma 2

BMP:

Bone morphogenic proteins

CH60:

Mitochondrial 60 kDa heat shock protein

CHFR:

Checkpoint with forkhead and ring finger domains

COF1:

Cofilin-1

ENOA:

α-Enolase

ER60:

Probable protein disulfide isomerase

ES:

Embryonic stem

FABP:

Liver fatty acid-binding protein

GTA1:

Glutathione S-transferase alpha

HDAC:

Histone deacetylase

HSP105:

Heat shock protein 105

KCRB:

Creatine kinase B

Mcl-1:

Myeloid cell leukemia 1

MDM2:

Murine double minute 2

MPSS:

Megasort and massively parallel signature sequencing

NDKA:

Nucleoside diphosphate kinase A

NPM2:

Nucleoplasmin 2

Oct4:

Octamer-binding transcription factor 4

PDCD6IP:

Programmed cell death six-interacting protein

PPARγ:

Peroxisome proliferator-activated receptor-γ

PS1:

Presenilin 1

RARs:

Retinoic acid receptors

RMS:

Rhabdomyosarcoma

SAHA:

Suberoylanilide hydroxamic acid

SIAH1:

Seven in absentia homologue 1

Sox2:

Sex-determining region Y-box 2

STAT3:

Signal transducer and activator of transcription 3

STI1:

Stress-inducible phosphoprotein 1

TACC3:

Transforming acidic coiled-coil protein 3

TCTP:

Translationally controlled tumor protein

TSAP:

Tumor suppressor-activated pathway

VDR:

Vitamin D receptor

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Authors and Affiliations

  1. Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128, Mainz, Germany

    Ean-Jeong Seo, Nicolas Fischer & Thomas Efferth

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  1. Ean-Jeong Seo
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  2. Nicolas Fischer
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  3. Thomas Efferth
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Correspondence to Thomas Efferth .

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Editors and Affiliations

  1. Bâtiment B2M, Institut Gustave Roussy, Villejuif, Val-de-Marne, France

    Adam Telerman

  2. Bâtiment B2M, Institut Gustave Roussy, Villejuif, Val-de-Marne, France

    Robert Amson

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Seo, EJ., Fischer, N., Efferth, T. (2017). Role of TCTP for Cellular Differentiation and Cancer Therapy. In: Telerman, A., Amson, R. (eds) TCTP/tpt1 - Remodeling Signaling from Stem Cell to Disease. Results and Problems in Cell Differentiation, vol 64. Springer, Cham. https://doi.org/10.1007/978-3-319-67591-6_14

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