Regulation of MRE11A by UBQLN4 leads to cisplatin resistance in patients with esophageal squamous cell carcinoma

Resistance to standard cisplatin‐based chemotherapies leads to worse survival outcomes for patients with esophageal squamous cell carcinoma (ESCC). Therefore, there is an urgent need to understand the aberrant mechanisms driving resistance in ESCC tumors. We hypothesized that ubiquilin‐4 (UBQLN4), a...

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Bibliographic Details
Published in:Molecular oncology 2021-04, Vol.15 (4), p.1069-1087
Main Authors: Murakami, Tomohiro, Shoji, Yoshiaki, Nishi, Tomohiko, Chang, Shu‐Ching, Jachimowicz, Ron D., Hoshimoto, Sojun, Ono, Shigeshi, Shiloh, Yosef, Takeuchi, Hiroya, Kitagawa, Yuko, Hoon, Dave S. B., Bustos, Matias A.
Format: Article
Language:English
Subjects:
5-Fluorouracil
Biopsy
Cancer therapies
Carrier Proteins - genetics
Cell Line, Tumor
chemoresistance
Chemotherapy
Cisplatin
Cisplatin - therapeutic use
Cloning
Committees
Deoxyribonucleic acid
DNA
DNA damage
DNA repair
Drug Resistance, Neoplasm
Endoscopy
Esophageal cancer
Esophageal Neoplasms - drug therapy
Esophageal Neoplasms - genetics
Esophageal Squamous Cell Carcinoma - drug therapy
Esophageal Squamous Cell Carcinoma - genetics
Esophagus
Experiments
Female
Genomes
Hospitals
Humans
Immunohistochemistry
Japan
Male
Meiosis
Middle Aged
Monoclonal antibodies
MRE11
MRE11 Homologue Protein - genetics
Mutation
neoadjuvant chemotherapy
Neoadjuvant Therapy
Nuclear Proteins - genetics
Patients
Polyclonal antibodies
Prognosis
Proteasomes
Proteins
Recombination
Squamous cell carcinoma
Surgery
Tumors
ubiquilin‐4
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Summary:Resistance to standard cisplatin‐based chemotherapies leads to worse survival outcomes for patients with esophageal squamous cell carcinoma (ESCC). Therefore, there is an urgent need to understand the aberrant mechanisms driving resistance in ESCC tumors. We hypothesized that ubiquilin‐4 (UBQLN4), a protein that targets ubiquitinated proteins to the proteasome, regulates the expression of Meiotic Recombination 11 Homolog A (MRE11A), a critical component of the MRN complex and DNA damage repair pathways. Initially, immunohistochemistry analysis was conducted in specimens from patients with ESCC (n = 120). In endoscopic core ESCC biopsies taken from 61 patients who underwent neoadjuvant chemotherapy (NAC) (5‐fluorouracil and cisplatin), low MRE11A and high UBQLN4 protein levels were associated with reduced pathological response to NAC (P 
ISSN:1574-7891
1878-0261
DOI:10.1002/1878-0261.12929