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Advances in Radiotherapy
& Nuclear Medicine Cripto-1 in cancer diagnosis and therapy

being the most common subtype, accounting for over
90% of cases. OSCC has a poor prognosis, with a 5-year
survival rate ranging between 50% and 55%. Similar
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to other malignancies, OSCC is driven by genetic and
environmental factors, and lymph node metastasis is a
key contributor to its poor outcomes. Investigating the
biological mechanisms underlying OSCC metastasis is
crucial for understanding its pathogenesis and identifying
potential therapeutic targets. Yoon et al. first reported an
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association between Cripto-1 and OSCC, demonstrating
high levels of membrane-bound Cripto-1 expression
in OSCC tissues. Their findings suggest that Criop-1
contributes to malignant transformation by promoting
tumor cell proliferation and migration. Jain et al. detected
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Cripto-1 in the serum of OSCC patients across various age
groups and genders, noting elevated levels during the early
stages of OSCC, which declined as the tumor progressed.
In contrast, another study found no significant variation in
Cripto-1 staining intensity across OSCC stages, although
Nodal expression (a Cripto-1 binding partner) did correlate
with tumor stage. This discrepancy may stem from the
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existence of two Cripto-1 isoforms: a soluble form present Figure 2. Molecular structure of Cripto-1 and tumor types with high
expression of the protein
in serum and a membrane-bound form detected in tissues. Abbreviations: CFC: Cripto-1-FRL-1-Cryptic; EGF: Epidermal growth
Figure 2 illustrates the structural complexity of Cripto-1 factor; GPI: Glycosylphosphatidylinositol.
and showcases the tumor types with high expression of Table 1. Cripto‑1‑associated tumor types and the implicated
this protein. To provide a comprehensive overview of signaling pathways
Cripto-1-related regulatory pathways and the supporting
experimental evidence, we have systemically compiled and Tumor type Signaling pathways Type of
summarized the relevant data in Table 1. This structured evidence
presentation not only enhances clarity regarding Cripto-1’s Breast cancer Notch pathway, PI3K/AKT pathway, In vitro, in vivo,
role in tumorigenesis but also provides a valuable reference and Wnt/β-catenin pathway and clinical
for comparative analysis and deeper investigation of this Cancers of the KRAS pathway, Src/Akt pathway, In vitro, in vivo,
important oncogenic biomarker. digestive system Activin/Amad3 pathway, TGF-β and clinical
pathway, and MAPK pathway
3. The value and challenges of Cripto-1 as a Lung cancer Notch pathway In vitro and
cancer diagnostic biomarker clinical
Liver cancer NF-κB/p65, Wnt/β-catenin In vitro, in vivo,
Tumor marker detection plays a critical role in the auxiliary pathway, and Nodal pathway and clinical
diagnosis of malignancies, aiding in the identification Ovarian cancer TGF-β pathway In vitro and
of primary tumor sites, tumor grading, and prognosis clinical
assessment. Cripto-1 has emerged as a promising Glioblastoma ErbB and MAPK pathway In vitro and
biomarker in this context; however, a critical appraisal of Multiforme clinical
the current literature reveals both its significant potential HNC Nodal pathway In vitro, in vivo,
and notable limitations. and clinical
Prostate cancer Wnt/β-catenin pathway and In vivo and
Cripto-1 is minimally expressed, or entirely absent, Nodal pathway clinical
in normal adult tissues but is significantly upregulated in
pre-cancerous lesions of the stomach, colon, and breast. Melanoma Nodal pathway, MAPK/ERK In vivo and
clinical
pathway, and Wnt/β-catenin
Its presence in the normal colonic mucosa of individuals pathway
with atrophic gastritis, Helicobacter pylori infection, or a Renal cell Wnt/β-catenin pathway In vivo, in vitro,
family history of colorectal cancer suggests an early role carcinoma and clinical
in carcinogenesis. Nonetheless, many of these findings Abbreviations: HNC: head and neck cancer; NF: nuclear factor;
are derived from small-scale studies, raising concerns TGF: transforming growth factor.

Volume 3 Issue 3 (2025) 87 doi: 10.36922/ARNM025130015