UbcH10 expression can predict prognosis and sensitivity to the antineoplastic treatment for colorectal cancer patients.
Colorectal cancer (CRC) is one of the most frequent and deadly malignancies worldwide. Despite the progresses made in diagnosis and treatment, the identification of tumor markers is still a strong clinical need, because current treatments are efficacious only in a subgroup of patients. UbcH10 represents a potential candidate biomarker, whose expression levels could be employed to predict response or resistance to chemotherapy or targeted agents. UbcH10 mRNA and protein expression levels have been evaluated in a large group of CRC patients and correlated with clinico-pathological characteristics, including KRAS mutations. Moreover, the endogenous levels of UbcH10 and its role on cell growth have been evaluated in CRC cells. Finally, to investigate the impact of UbcH10 protein expression on the response to irinotecan, its active metabolite SN-38 and cetuximab treatment, UbcH10 silencing experiments were carried-out on two colon carcinoma cell lines, Caco-2, and DLD1. Overexpression of UbcH10 mRNA and protein was observed in the vast majority of patients analyzed. UbcH10 suppression decreased CRC cell growth rate (at least in part through deregulation of Cyclin B and ERK1) and sensitized them to pharmacological treatments with irinotecan, SN-38 and cetuximab (at least in part through a down-regulation of AKT). Taken together, these findings indicate that UbcH10 expression regulates CRC growth and could play an important role in the personalization of the therapy of CRC patients.
Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Department of Molecular Medicine and Medical Biotechnology (DMMBM), University of Naples "Federico II", Via S. Pansini 5, Naples, Italy.
Nunzio Antonio
NA
Cacciola
Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Department of Molecular Medicine and Medical Biotechnology (DMMBM), University of Naples "Federico II", Via S. Pansini 5, Naples, Italy.
Chiara
C
Calabrese
Department of Public Health, University of Naples "Federico II", Via S. Pansini 5, Naples, Italy.
Umberto
U
Malapelle
Unit of General Surgery, Second University of Naples, Piazza Miraglia 2, Naples, Italy.
Gianluca
G
Pellino
Department of Clinical Medicine and Surgery, University of Naples "Federico II", Via S. Pansini 5, Naples, Italy.
Alfonso
A
De Stefano
Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Department of Molecular Medicine and Medical Biotechnology (DMMBM), University of Naples "Federico II", Via S. Pansini 5, Naples, Italy.
Romina
R
Sepe
Department of Public Health, University of Naples "Federico II", Via S. Pansini 5, Naples, Italy.
Roberta
R
Sgariglia
Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Department of Molecular Medicine and Medical Biotechnology (DMMBM), University of Naples "Federico II", Via S. Pansini 5, Naples, Italy.|Institute of Pathology, Molecular Pathology Division, University of Basel, Schonbeinstrasse 40, Basel, Switzerland.
Cristina
C
Quintavalle
Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Department of Molecular Medicine and Medical Biotechnology (DMMBM), University of Naples "Federico II", Via S. Pansini 5, Naples, Italy.
Antonella
A
Federico
Department of Public Health, University of Naples "Federico II", Via S. Pansini 5, Naples, Italy.
Antonio
A
Bianco
Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Department of Molecular Medicine and Medical Biotechnology (DMMBM), University of Naples "Federico II", Via S. Pansini 5, Naples, Italy.|Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Federal University of São Paulo, São Paulo, Brazil.
André
A
Uchimura Bastos
Department of Advanced Biomedical Sciences, University of Naples "Federico II", Via S. Pansini 5, Naples, Italy.
Marco
M
Milone
Department of Public Health, University of Naples "Federico II", Via S. Pansini 5, Naples, Italy.
Claudio
C
Bellevicine
Department of Advanced Biomedical Sciences, University of Naples "Federico II", Via S. Pansini 5, Naples, Italy.
Francesco
F
Milone
Department of Clinical Medicine and Surgery, University of Naples "Federico II", Via S. Pansini 5, Naples, Italy.
Chiara
C
Carlomagno
Unit of General Surgery, Second University of Naples, Piazza Miraglia 2, Naples, Italy.
Francesco
F
Selvaggi
Department of Public Health, University of Naples "Federico II", Via S. Pansini 5, Naples, Italy.
Giancarlo
G
Troncone
Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Department of Molecular Medicine and Medical Biotechnology (DMMBM), University of Naples "Federico II", Via S. Pansini 5, Naples, Italy.|National Cancer Institute-INCA, Rua André Cavalcanti, 37-Centro, CEP 20231-050, Rio de Janeiro, Brazil.
Alfredo
A
Fusco
Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Department of Molecular Medicine and Medical Biotechnology (DMMBM), University of Naples "Federico II", Via S. Pansini 5, Naples, Italy.
Pierlorenzo
P
Pallante
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D018938:Caco-2 Cells; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000068818:Cetuximab / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics* / Q000378:metabolism*
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000077146:Irinotecan; C105156:UBE2C protein, human; D044763:Ubiquitin-Conjugating Enzymes; D000068818:Cetuximab; D002166:Camptothecin
KRAS; UbcH10; cetuximab; colorectal cancer; irinotecan