Radiosensitivity of Cancer Cells Is Regulated by Translationally Controlled Tumor Protein.

Jiwon Jung,Ji-Sun Lee,Kyunglim Lee,Yun-Sil Lee

doi:10.3390/cancers11030386

Jiwon Jung, Ji-Sun Lee + Show 2 more

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https://doi.org/10.3390/cancers11030386

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Journal: Cancers	Publication Date: Mar 19, 2019
Citations: 15	License type: CC BY 4.0

Affiliation: Ewha Womans University

Abstract

Translationally controlled tumor protein (TCTP) is a ubiquitous multifunctional protein that is essential for cell survival. This study reveals that the regulation of radiosensitivity of cancer cells is yet another function of TCTP. The relationship between endogenous TCTP levels and sensitivity to radiation was examined in breast cancer cell lines (T47D, MDA-MB-231, and MCF7) and lung cancer cells lines (A549, H1299, and H460). Cancer cells with high expression levels of TCTP were more resistant to radiation. TCTP overexpression inhibited radiation-induced cell death, while silencing TCTP led to an increase in radiosensitivity. DNA damage in the irradiated TCTP-silenced A549 cells was greater than in irradiated control shRNA-transfected A549 cells. p53, a well-known reciprocal regulator of TCTP, was increased in irradiated TCTP down-regulated A549 cells. Moreover, introduction of p53 siRNA in TCTP knocked-down A549 cells abrogated the increased radiosensitivity induced by TCTP knockdown. An in vivo xenograft study also confirmed enhanced radiosensitivity in TCTP down-regulated A549 cells. These findings suggest that TCTP has the potential to serve as a therapeutic target to overcome radiation resistance in cancer, a major problem for the effective treatment of cancers.

Highlights

Radiation therapy (RT) is an important treatment option for cancer therapy, where it can be used alone or in combination with chemotherapies
We investigated whether the expression of Translationally controlled tumor protein (TCTP) regulates the sensitivity to irradiation in breast and lung cancer cells
[12], we is well known that TCTP plays an important role in DNA damage sensing and repair [12], we examined whether radiation-induced damage was increased after TCTPafter shRNA

Summary

Introduction

Radiation therapy (RT) is an important treatment option for cancer therapy, where it can be used alone or in combination with chemotherapies. Acquired radioresistance of tumor cells during radiation treatment can limit the usefulness of RT [2]. The mechanism behind resistance of cancer cells to RT remains largely elusive. Controlling the radioresistance of cancer cells is important for successful RT. Controlled tumor protein (TCTP) is a highly conserved protein present in all eukaryotic cells. TCTP has been implicated in important cellular process, such as cell growth, apoptosis, DNA damage repair, tumorigenesis, cancer progression, and protection against various stress conditions [3]. TCTP appears to be one of important factors for tumor reversion, in which v-Src-transfected NIH3T3 cells returned to their normal phenotype after TCTP down-regulation [9]

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