Cripto-1: an extracellular protein – connecting the sequestered biological dots

Klauzinska, Malgorzata; Bertolette, Daniel C.; Tippireddy, Sudhamsh; Strizzi, Luigi; Gray, Peter C.; Gonzales, Mónica; Duroux, Meg; Ruvo, Menotti; Wechselberger, Christian; Castro, Nadia P.; Rangel, Maria Cristina; Focà, Annalia; Sandomenico, Annamaria; Hendrix, Mary J.C.; Salomon, David; Cuttitta, Frank

doi:10.3109/03008207.2015.1077239

Cited by 12 publications

(17 citation statements)

References 53 publications

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“…ACVR1B-645H,) were purchased from the indicated vendors. CR1/BP interaction assays were run in parallel to that described previously by Klauzinska and colleagues (19). In brief, four different target proteins (Nodal, GRP78, ACVR1B/Alk4, and BSA) were solid phased to a 96-well plate (Costar, catalog no.…”

Section: Ihc Staining and Scoringmentioning

confidence: 99%

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Sulforaphane Suppresses the Growth of Triple-negative Breast Cancer Stem-like Cells In vitro and In vivo

Castro

Rangel

Merchant

et al. 2019

Cancer Prevention Research

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Triple-negative breast cancer (TNBC) represents the poorest prognosis among all of breast cancer subtypes with no currently available effective therapy. In this study, we hypothesized that sulforaphane, a dietary component abundant in broccoli and its sprouts, can inhibit malignant cell proliferation and tumor sphere formation of cancer stem-like cells (CSC) in TNBC. CSC population was isolated using FACS analysis with the combined stem cell surface markers, CD44 þ /CD24 À / CD49f þ. The effect of sulforaphane on a stem-related embryonic oncogene CRIPTO-1/TDGF1 (CR1) was evaluated via ELISA. In vivo, BalbC/nude mice were supplemented with sulforaphane before and after TNBC cell inoculation (daily intraperitoneal injection of 50 mg sulforaphane/kg for 5 and 3 weeks, respectively), and the effects of sulforaphane during mamma-ry tumor initiation and growth were accessed with NanoString gene analysis. We found that sulforaphane can inhibit cell proliferation and mammosphere formation of CSCs in TNBC. Further analysis of gene expression in these TNBC tumor cells revealed that sulforaphane significantly decreases the expression of cancer-specific CR1, CRIPTO-3/TDGF1P3 (CR3, a homologue of CR1), and various stem cell markers including Nanog, aldehyde dehydrogenase 1A1 (ALDH1A1), Wnt3, and Notch4. Our results suggest that sulforaphane may control the malignant proliferation of CSCs in TNBC via Cripto-mediated pathway by either suppressing its expression and/or by inhibiting Cripto/Alk4 protein complex formation. Thus, the use of sulforaphane for chemoprevention of TNBC is plausible and warrants further clinical evaluation.

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Section: Ihc Staining and Scoringmentioning

confidence: 99%

“…ab103891), and 50 mL goat anti-rabbit IgG-HRP (Santa Cruz Biotechnology, catalog no. sc-2004) according to the procedure published previously (19). A PBS wash and 30-minute room temperature rotary shaker incubation was performed between each treatment following CR1 addition.…”

Section: Ihc Staining and Scoringmentioning

confidence: 99%

Sulforaphane Suppresses the Growth of Triple-negative Breast Cancer Stem-like Cells In vitro and In vivo

Castro

Rangel

Merchant

et al. 2019

Cancer Prevention Research

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“…Cripto-1 and Cryptic mediate the binding of GDF1 and GDF3 to the same receptors as Nodal, whereas other TGFβ superfamily ligands such as Activin-βA and –βB can signal through Alk4 and ActRIIA or ActRIIB without co-receptor requirement but are inhibited by the presence of Cripto-1 [7, 22–26]. Therefore, Cripto-1/Cryptic mediate signaling specificity among TGFβ superfamily ligands and Cripto-1 is also capable of inducing signaling of other pathways [27–32]. Of note however, although Cripto-1 involvement in Nodal signaling is well established, Cripto-1 independent signaling by Nodal has also been demonstrated.…”

Section: Canonical Nodal Signaling and Biological Rolesmentioning

confidence: 99%

Plasticity underlies tumor progression: role of Nodal signaling

Bodenstine

Chandler

Seftor

et al. 2016

Cancer Metastasis Rev

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The transforming growth factor beta (TGFβ) superfamily member Nodal is an established regulator of early embryonic development, with primary roles in endoderm induction, left-right asymmetry and primitive streak formation. Nodal signals through TGFβ family receptors at the plasma membrane and induces signaling cascades leading to diverse transcriptional regulation. While conceptually simple, the regulation of Nodal and its molecular effects are profoundly complex and context dependent. Pioneering work by developmental biologists has characterized the signaling pathways, regulatory components, and provided detailed insight into the mechanisms by which Nodal mediates changes at the cellular and organismal levels. Nodal is also an important factor in maintaining pluripotency of embryonic stem cells through regulation of core transcriptional programs. Collectively, this work has led to an appreciation for Nodal as a powerful morphogen capable of orchestrating multiple cellular phenotypes. Although Nodal is not active in most adult tissues, its re-expression and signaling have been linked to multiple types of human cancer, and Nodal has emerged as a driver of tumor growth and cellular plasticity. In vitro and in vivo experimental evidence has demonstrated that inhibition of Nodal signaling reduces cancer cell aggressive characteristics, while clinical data have established associations with Nodal expression and patient outcomes. As a result, there is great interest in the potential targeting of Nodal activity in a therapeutic setting for cancer patients that may provide new avenues for suppressing tumor growth and metastasis. In this review, we evaluate our current understanding of the complexities of Nodal function in cancer and highlight recent experimental evidence that sheds light on the therapeutic potential of its inhibition.

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“…14,22 However, here we have shown that cripto-1 antibodies available commercially provide different results, pending cell type, downstream processing (such as fixation) and cellular assay. 14,22 However, here we have shown that cripto-1 antibodies available commercially provide different results, pending cell type, downstream processing (such as fixation) and cellular assay.…”

Section: Discussionmentioning

confidence: 77%

“…[4][5][6][7] In the healthy adult, cripto-1 expression has been suggested to be turned off or, in some cases, reduced to only a small population of adult stem cells. 14 Detection of cripto-1 as a cancer biomarker relies on the specificity and sensitivity of the different cripto-1 antibodies. 3,[10][11][12][13] Due to the seemingly low expression of cripto-1 in healthy individuals and that it might be highly re-expressed in cancer cells, cripto-1 has become a popular subject in biomarker discovery in various cancers.…”

Section: Introductionmentioning

confidence: 99%

An evaluation of different Cripto‐1 antibodies and their variable results

Gudbergsson

Duroux

2019

J of Cellular Biochemistry

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Cripto‐1 is a protein expressed during embryonal development and has been linked to several malignant processes in cancer. Since the discovery of cripto‐1 in the late 1980s, it has become a subject of biomarker investigation in several types of cancer which in many cases relies on immunolocalization of cripto‐1 using antibodies. Investigating cripto‐1 expression and localization in primary glioblastoma cells, we discovered nonspecific binding of cripto‐1 antibody to the extracellular matrix Geltrex. A panel of four cripto‐1 antibodies was investigated with respect to their binding to the Geltrex matrix and to the cripto‐1 positive control cells NTERA2. The cripto‐1 expression was varied for the different antibodies with respect to cellular localization and fixation methods. To further elaborate on these findings, we present a systematic review of cripto‐1 antibodies found in the literature and highlight some possible cross reactants with data on sequence alignments and structural comparison of EGF domains.

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Cripto-1: an extracellular protein – connecting the sequestered biological dots

Cited by 12 publications

References 53 publications

Sulforaphane Suppresses the Growth of Triple-negative Breast Cancer Stem-like Cells In vitro and In vivo

Sulforaphane Suppresses the Growth of Triple-negative Breast Cancer Stem-like Cells In vitro and In vivo

Plasticity underlies tumor progression: role of Nodal signaling

An evaluation of different Cripto‐1 antibodies and their variable results

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