New Insights into Cancer Targeted Therapy: Nodal and Cripto-1 as Attractive Candidates

Abstract

The transforming growth factor beta (TGF-β) signaling is fundamental for correct embryonic development. However, alterations of this pathway have been correlated with oncogenesis, tumor progression and sustaining of cancer stem cells (CSCs). Cripto-1 (CR-1) and Nodal are two embryonic proteins involved in TGF-β signaling. Their expression is almost undetectable in terminally differentiated cells, but they are often re-expressed in tumor cells, especially in CSCs. Moreover, cancer cells that show high levels of CR-1 and/or Nodal display more aggressive phenotypes in vitro, while in vivo their expression correlates with a worse prognosis in several human cancers. The ability to target CSCs still represents an unmet medical need for the complete eradication of certain types of tumors. Given the prognostic role and the selective expression of CR-1 and Nodal on cancer cells, they represent archetypes for targeted therapy. The aim of this review is to clarify the role of CR-1 and Nodal in cancer stem populations and to summarize the current therapeutic strategy to target CSCs using monoclonal antibodies (mAbs) or other molecular tools to interfere with these two proteins.

Immune-related gene signature associates with immune landscape and predicts prognosis accurately in patients with Wilms tumour

“…NODAL is an embryonic protein involved in TGF-b signaling and is highly expressed in various cancers. Cancer cells with high levels of NODAL displayed a more aggressive phenotype in vitro, while in vivo was associated with a poorer prognosis in several human cancers, highlighting it as a potential target and marker for targeted cancer therapy (70)(71)(72). Previous studies have also identified a novel link between OXT and cancer.…”

Profiling and targeting cancer stem cell signaling pathways for cancer therapeutics

“…Consistent with Nodal’s role in embryogenesis, Activin/Nodal signaling maintains pluripotency in stem cells through induction of Nanog and other cell cycle factors ( Pauklin and Vallier, 2015 ). Cripto-1 is similar to Nodal in that it is an embryonic protein involved in TGF-β signaling ( Arboretto et al, 2021 ). Both Cripto-1 and Nodal have minimal expression in terminally differentiated cells, but are often re-expressed in CSCs and in a dose-dependent manner can trigger more aggressive phenotypes and worsened prognosis for several cancer-subtypes ( Arboretto et al, 2021 ).…”

“…Cripto-1 is similar to Nodal in that it is an embryonic protein involved in TGF-β signaling ( Arboretto et al, 2021 ). Both Cripto-1 and Nodal have minimal expression in terminally differentiated cells, but are often re-expressed in CSCs and in a dose-dependent manner can trigger more aggressive phenotypes and worsened prognosis for several cancer-subtypes ( Arboretto et al, 2021 ).…”

“…Other studies, which not only block the TGF-β Nodal/Activin Alk4/7 receptor but also simultaneously inhibit the Hh pathway, abolish CSC’s self-renewal capacity and render CSCs more susceptible to gemcitabine in vivo ( Lonardo et al, 2011 ). Monoclonal antibodies that interfere with TGF-β proteins Cripto-1 or Nodal in vitro have also shown promising effects at abrogating CSCs ( Arboretto et al, 2021 ). Moreover, SB431542, a SMI, partially reversed Nodal-induced chemoresistance in melanoma CSCs, in vitro ( Li et al, 2018b ).…”

Caracterización de la pérdida del gen NOMO1 en cáncer colorrectal

“…Se cree que son las células iniciadoras del cáncer, así como el origen de las recaídas. Otra característica difundida en las CSC, pero no limitada a ellas, es la reactivación de algunas vías de señalización embriogénicas que son fundamentales para las células madre "normales" 174 . Esto suele deberse a la expresión aberrante de algunas proteínas implicadas en vías de señalización que suelen estar activas en las células embrionarias.…”