Dataset Information

TIPRL1 and its ATM-dependent phosphorylation modulate the DNA Damage Response to promote radiotherapy resistance in head and neck cancer

ABSTRACT: TIPRL1 (target of rapamycin signaling pathway regulator-like 1) is a known interactor and inhibitor of protein phosphatases PP2A, PP4 and PP6 – all pleiotropic modulators of the DNA Damage Response (DDR). Here, we describe a new role for TIPRL1 in the radiotherapy (RT) response of Head and Neck Squamous Cell Carcinoma (HNSCC). TIPRL1 expression was found increased in tumor versus non-tumor tissue, with high tumoral TIPRL1 expression associating with lower locoregional control and decreased survival of RT-treated patients. TIPRL1 deletion in SQD9 cells resulted in increased RT sensitivity, a faster cell cycle arrest, increased micronuclei formation and an altered proteome-wide DDR. Upon irradiation, ATM phosphorylates TIPRL1 at Ser265, contributing to TIPRL1-mediated RT resistance. Mass spectrometry analysis identified DNA-PKcs, RAD51 and nucleosomal histones as novel TIPRL1 interactors in irradiated cells. Histone binding, although stimulated by RT, was adversely affected by TIPRL1 Ser265 phosphorylation. Our findings underscore a clinically relevant role for TIPRL1 and its ATM-dependent phosphorylation in RT resistance through modulation of DNA damage checkpoint activation and repair.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Oral Mucosa Squamous Cell, Cell Culture

DISEASE(S): Head And Neck Cancer

SUBMITTER: Rita Derua

LAB HEAD: Prof. Dr. Veerle Janssens

PROVIDER: PXD044931 | Pride | 2025-05-07

REPOSITORIES: Pride

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			Action	DRS
	2022_10_15_24_AM_File_Size_669483950_Byte_F040066.mzid.gz	Mzid
	2022_10_15_24_AM_File_Size_669483950_Byte_F040066.mzid_2022_10_15_24_AM_File_Size_669483950_Byte_F040066.MGF	Mzid
	2022_10_21_50_PM_File_Size_658418589_Byte_F040046.mzid.gz	Mzid
	2022_10_21_50_PM_File_Size_658418589_Byte_F040046.mzid_2022_10_21_50_PM_File_Size_658418589_Byte_F040046.MGF	Mzid
	2022_11_59_15_PM_File_Size_631613497_Byte_F040062.mzid.gz	Mzid

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TIPRL1 and its ATM-dependent phosphorylation promote radiotherapy resistance in head and neck cancer.

Cokelaere Célie C Dok Rüveyda R Cortesi Emanuela E EE Zhao Peihua P Sablina Anna A Nuyts Sandra S Derua Rita R Janssens Veerle V

Cellular oncology (Dordrecht, Netherlands) 20231116 3

<h4>Purpose</h4>TIPRL1 (target of rapamycin signaling pathway regulator-like 1) is a known interactor and inhibitor of protein phosphatases PP2A, PP4 and PP6 - all pleiotropic modulators of the DNA Damage Response (DDR). Here, we investigated the role of TIPRL1 in the radiotherapy (RT) response of Head and Neck Squamous Cell Carcinoma (HNSCC).<h4>Methods</h4>TIPRL1 mRNA (cBioportal) and protein expression (immunohistochemistry) in HNSCC samples were linked with clinical patient data. TIPRL1-depl ...[more]

PMID: 37971644

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