Overexpression of transferrin receptor CD71 and its tumorigenic properties in esophageal squamous cell carcinoma

Abstract

Esophageal squamous cell carcinoma (ESCC) is the predominant type of esophageal cancer in endemic Asian regions. In the present study, we investigated the clinical implication and role of transferrin receptor CD71 in ESCC. CD71 has a physiological role in cellular iron intake and is implicated in the carcinogenesis of various types of tumors. In our cohort, more than a 2-fold upregulation of the CD71 transcript was detected in 61.5% of patients using quantitative polymerase chain reaction. Immunohistochemical analysis also showed strong membranous and cytoplasmic localization of CD71 in paraffin-embedded tumors. Staining parallel tumor sections with the proliferative marker Ki-67 revealed that the pattern of Ki-67 staining was associated with CD71 expression. Analysis of clinicopathological data indicated that CD71 overexpression can be used as an indicator for advanced T4 stage (p=0.0307). These data suggested a strong link between CD71 and ESCC. Subsequent in vitro assays using short interfering RNA (siRNA) to suppress CD71 expression confirmed the tumorigenic properties of CD71 in ESCC; cell growth inhibition and cell cycle arrest at S phase were observed in CD71-suppressed cells. The underlying mechanism involved activation of the MEK/ERK pathway. In summary, the present study provides evidence showing the tumorigenic properties of CD71 in ESCC with clinical correlations and suggests targeting CD71 as a strategy for the treatment of ESCC.

CD71+ Population Enriched by HPV-E6 Protein Promotes Cancer Aggressiveness and Radioresistance in Cervical Cancer Cells

“…Our findings provided additional evidence indicating that CD71 protein is highly expressed in cervical cancer. Increased expression of CD71 has also been reported in many other cancers, including astrocytic brain tumors, breast cancer, cholangiocarcinoma, ESCC, pancreatic cancer, and renal cell carcinoma (17)(18)(19)(20)(21)(22). Furthermore, enhanced CD71 expression has been reported to be correlated with poor clinical outcomes in patients with estrogen receptor-positive breast cancer and glioblastoma, suggesting that CD71 might serve as a therapeutic target (21,22).…”

“…CD71, also known as transferrin receptor, is a homodimeric transmembrane glycoprotein that binds to iron-bound transferrin and serves as a mediator for the delivery of extracellular iron into cells via endocytosis (15,16). Overexpression of CD71 has been reported in certain types of solid tumors, including breast cancer, renal cell carcinoma, cholangiocarcinoma, esophageal squamous cell carcinoma (ESCC), pancreatic cancer, and glioblastoma (17)(18)(19)(20)(21)(22). High levels of CD71 are also detected in leukemic cells of poorly differentiated acute myeloid leukemia (AML) compared with the levels in partially differentiated AML (23).…”

Regulation of transferrin receptor-1 mRNA by the interplay between IRE-binding proteins and miR-7/miR-141 in the 3′-IRE stem–loops

“…Higher expression of TfR1 allows cells to utilize more iron for cell proliferation and metabolism. Indeed some types of cancer cells express elevated levels of TfR1 (Ryschich et al 2004;Prutki et al 2006;Habashy et al 2010;Chan et al 2014), although the mechanisms behind TfR1 overexpression in cancer cells may be complex and not well characterized. As a fraction of TfR1 mRNA devoid of IRPs binding can be constantly attacked by miR-7-5p or miR-141-3p, we investigated whether expression levels of these miRNAs may correlate with TfR1 mRNA expression in cancers.…”

A stemness-related seven-gene signature for predicting prognosis and treatment response in muscle invasive bladder cancer

“…TFRC (transferrin receptor), also known as CD71, is an important regulator for iron metabolism in cancers. CD71 is frequently upregulated and indicate aggressive phenotype as well as poor clinical outcome in esophageal squamous cell carcinoma [44] and breast cancer [45]. Expression of CD71 was closely related to the staining of proliferative marker Ki-67 and CD71-suppressed tumor cells exhibit cell growth inhibition and cell cycle arrest at S phase [44].…”

“…CD71 is frequently upregulated and indicate aggressive phenotype as well as poor clinical outcome in esophageal squamous cell carcinoma [44] and breast cancer [45]. Expression of CD71 was closely related to the staining of proliferative marker Ki-67 and CD71-suppressed tumor cells exhibit cell growth inhibition and cell cycle arrest at S phase [44]. CD71 is also regarded as a phenotypic marker of cancer stem-like cells in cervical cancer [46].…”