Transferrin receptor 1 overexpression is associated with tumour de‐differentiation and acts as a potential prognostic indicator of hepatocellular carcinoma

Adachi, Makiko; Kai, Keita; Yamaji, Koutaro; Ide, Takao; Noshirο, Hirokazu; Kawaguchi, Atsushı; Aishima, Shinichi

doi:10.1111/his.13847

Cited by 55 publications

(41 citation statements)

References 33 publications

(56 reference statements)

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“…When there is a lack of α1-AT, iron uptake through transferrin binding with TfR1 will not be inhibited, causing the expression of free TfR1 to decrease. The correlation of TfR1 expression with clinicopathological features of CRC might be different from other types of tumors 42,43. Iron plays a complex role in CRC.…”

Section: Discussionmentioning

confidence: 92%

<p>Downregulation of TfR1 promotes progression of colorectal cancer via the JAK/STAT pathway</p>

Cui¹,

Cheng²,

Liang³

et al. 2019

CMAR

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Background: Colorectal cancer (CRC) is one of the most prevalent gastrointestinal malignancies. The incidence of CRC has been rapidly increasing in China. Transferrin receptor 1 (TfR1) is a key regulator of cellular iron homeostasis. Several studies have demonstrated TfR1 overexpression in a variety of human tumors, but the association between TfR1 and CRC remains unclear. Methods: TfR1 expression was evaluated in six CRC cell lines and tumor tissues. A total of 201 CRC patients were included for immunohistochemistry and 19 pairs of frozen tissues were used for real-time PCR. Cell proliferation, cell cycle, cell migration and invasion, and in vivo carcinogenesis were tested after downregulation of TfR1 by lentivirus. Protein microarray and Western blot analyses were used to explore the underlying mechanisms of TfR1 in CRC. Results: TfR1 expression was higher in CRC tissues than in normal tissues (57.2% vs 22.9%, P ＜0.001). TfR1 expression was obviously higher in CRC tissues with well differentiation ( P ＝0.008), no lymph node metastasis ( P ＝0.002), no distant metastasis ( P ＝0.006), no vascular invasion ( P ＜0.001) and early TNM stage ( P ＝0.013). CRC patients with TfR1-positive expression had a better survival than those with TfR1-negative expression ( P ＝0.044). Downregulation of TfR1 expression inhibited cell proliferation, promoted cells from G1 phase to S phase and facilitated cell migration and invasion. Knockdown of TfR1 also suppressed tumor growth in BALB/C-nu mice. Protein microarray and Western blot analyses showed that the Janus protein tyrosine kinase/signal transducer and activator of transcription pathway was activated along with downregulation of TfR1 expression. Conclusion: Though TfR1 was overexpressed in colorectal cancer tissues, there was evidence that downregulation of TfR1 could promote cancer progression.

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Section: Discussionmentioning

confidence: 92%

<p>Downregulation of TfR1 promotes progression of colorectal cancer via the JAK/STAT pathway</p>

Cui¹,

Cheng²,

Liang³

et al. 2019

CMAR

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“…In fact, TfR1 has been identified as a universal cancer marker (55). Increased expression of TfR1 correlates with advanced stage and/or poorer prognosis in a number of cancers, including solid cancers such as esophageal squamous cell carcinoma (56), breast cancer (57, 58), ovarian cancer (59), lung cancer (60), cervical cancer (61), bladder cancer (62), osteosarcoma (63), pancreatic cancers (64), cholangiocarcinoma (65), renal cell carcinoma (66), hepatocellular carcinoma (67,68), adrenal cortical carcinoma (69), and cancers of the nervous system (70) as well as hematopoietic malignancies such as acute lymphoblastic leukemia (ALL) (71,72), chronic lymphocytic leukemia (CLL) (73), and non-Hodgkin lymphoma (NHL) (73,74). Interestingly, patients infected with the human immunodeficiency virus (HIV) often develop more aggressive NHL that have been shown to express even higher levels of TfR1 messenger RNA compared to NHL cells from non-infected patients (75,76).…”

Section: Tfr1 Expression In Normal and Cancer Cellsmentioning

confidence: 99%

Antibodies Targeting the Transferrin Receptor 1 (TfR1) as Direct Anti-cancer Agents

et al. 2021

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The transferrin receptor 1 (TfR1), also known as cluster of differentiation 71 (CD71), is a type II transmembrane glycoprotein that binds transferrin (Tf) and performs a critical role in cellular iron uptake through the interaction with iron-bound Tf. Iron is required for multiple cellular processes and is essential for DNA synthesis and, thus, cellular proliferation. Due to its central role in cancer cell pathology, malignant cells often overexpress TfR1 and this increased expression can be associated with poor prognosis in different types of cancer. The elevated levels of TfR1 expression on malignant cells, together with its extracellular accessibility, ability to internalize, and central role in cancer cell pathology make this receptor an attractive target for antibody-mediated therapy. The TfR1 can be targeted by antibodies for cancer therapy in two distinct ways: (1) indirectly through the use of antibodies conjugated to anti-cancer agents that are internalized by receptor-mediated endocytosis or (2) directly through the use of antibodies that disrupt the function of the receptor and/or induce Fc effector functions, such as antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), or complement-dependent cytotoxicity (CDC). Although TfR1 has been used extensively as a target for antibody-mediated cancer therapy over the years, interest continues to increase for both targeting the receptor for delivery purposes and for its use as direct anti-cancer agents. This review focuses on the developments in the use of antibodies targeting TfR1 as direct anti-tumor agents.

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“…Iron metabolism pathways, including processes of uptake-export, storage, and regulation, may be abnormally regulated during cancer progression (19). For example, transferrin receptor 1 (TFR1) is involved in the regulation of iron uptake and cell growth, is abnormally expressed in tumors and is closely related to tumor proliferation and metastasis (20)(21)(22). However, current studies mainly focus on the role of iron metabolism in cancer development and treatment and rarely discuss the role of iron metabolism genes in cancer prognosis (23,24).…”

Section: Discussionmentioning

confidence: 99%

Identification of Iron Metabolism-Related Gene Signatures for Predicting the Prognosis of Patients With Sarcomas

et al. 2021

Front. Oncol.

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Iron is one of the essential trace elements in the human body. An increasing amount of evidence indicates that the imbalance of iron metabolism is related to the occurrence and development of cancer. Here, we obtained the gene expression and clinical data of sarcoma patients from TCGA and the GEO database. The prognostic value of iron metabolism-related genes (IMRGs) in patients with sarcoma and the relationship between these genes and the immune microenvironment were studied by comprehensive bioinformatics analyses. Two signatures based on IMRGs were generated for the overall survival (OS) and disease-free survival (DFS) of sarcoma patients. At 3, 5, and 7 years, the areas under the curve (AUCs) of the OS signature were 0.708, 0.713, and 0.688, respectively. The AUCs of the DFS signature at 3, 5, and 7 years were 0.717, 0.689, and 0.702, respectively. Kaplan–Meier survival analysis indicated that the prognosis of high-risk patients was worse than that of low-risk patients. In addition, immunological analysis showed that there were different patterns of immune cell infiltration among patients in different clusters. Finally, we constructed two nomograms that can be used to predict the OS and DFS of sarcoma patients. The C-index was 0.766 (95% CI: 0.697–0.835) and 0.763 (95% CI: 0.706–0.820) for the OS and DFS nomograms, respectively. Both the ROC curves and the calibration plots showed that the two nomograms have good predictive performance. In summary, we constructed two IMRG-based prognostic models that can effectively predict the OS and DFS of sarcoma patients.

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Transferrin receptor 1 overexpression is associated with tumour de‐differentiation and acts as a potential prognostic indicator of hepatocellular carcinoma

Cited by 55 publications

References 33 publications

<p>Downregulation of TfR1 promotes progression of colorectal cancer via the JAK/STAT pathway</p>

<p>Downregulation of TfR1 promotes progression of colorectal cancer via the JAK/STAT pathway</p>

Antibodies Targeting the Transferrin Receptor 1 (TfR1) as Direct Anti-cancer Agents

Identification of Iron Metabolism-Related Gene Signatures for Predicting the Prognosis of Patients With Sarcomas

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