Cripto-1 as a Key Factor in Tumor Progression, Epithelial to Mesenchymal Transition and Cancer Stem Cells

Arnouk, Hilal; Yum, Gloria; Shah, Dean

doi:10.3390/ijms22179280

Cited by 9 publications

(6 citation statements)

References 70 publications

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“…However, subsequent studies with the third generation EGFR TKI osimertinib showed that CRIPTO was ineffective in eliciting drug resistance, although CRIPTO serum levels mirrored patient progression and resistance to treatment ( 32 ). Altogether, these findings highlight a complex role of CRIPTO in regulating tumor stemness that deserves further investigation, also in light of potential CRIPTO targeting by molecular and immunotherapeutic strategies ( 33 , 34 ). Here, we show that CRIPTO is dynamically expressed in NSCLC spheroid cultures derived from surgical specimens of lung adenocarcinoma (AC) and squamous cell carcinoma (SCC).…”

Section: Introductionmentioning

confidence: 78%

CRIPTO Is a Marker of Chemotherapy-Induced Stem Cell Expansion in Non-Small Cell Lung Cancer

Francescangeli

Angelis²,

Rossi³

et al. 2022

Front. Oncol.

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Chemotherapy is the mainstay for the treatment of non-small cell lung cancer (NSCLC). However, NSCLC cells are either intrinsically chemoresistant or rapidly develop therapy resistance. Cancer stem cells (CSCs) are widely recognized as the cell population responsible for resistance to systemic therapies, but the molecular responses of CSCs to chemotherapeutic agents are largely unknown. We identified the embryonic protein CRIPTO in stem cell-enriched spheroid cultures of adenocarcinoma (AC) and squamous cell carcinoma (SCC) derived from NSCLC surgical specimens. The CRIPTO-positive population had increased clonogenic capacity and expression of stem cell-related factors. Stemness-related properties were also obtained with forced CRIPTO expression, whereas CRIPTO downregulation resulted in cell cycle blockade and CSCs death. Cell populations positive and negative for CRIPTO expression were interconvertible, and interfering with their reciprocal equilibrium resulted in altered homeostasis of cell expansion both in spheroid cultures and in tumor xenografts. Chemotherapy treatment of NSCLC cells resulted in reduction of cell number followed by increased CRIPTO expression and selective survival of CRIPTO-positive cells. In NSCLC tumor xenografts, chemotherapeutic agents induced partial cell death and tumor stabilization followed by CRIPTO overexpression and tumor progression. Altogether, these findings indicate CRIPTO as a marker of lung CSCs possibly implicated in cancer cell plasticity and post-chemotherapy tumor progression.

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Section: Introductionmentioning

confidence: 78%

CRIPTO Is a Marker of Chemotherapy-Induced Stem Cell Expansion in Non-Small Cell Lung Cancer

Francescangeli

Angelis²,

Rossi³

et al. 2022

Front. Oncol.

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“…Moreover, Cripto-1 is a protein essential for human development in the early phases of gastrulation and is also associated with healing processes. However, Cripto-1 is upregulated in most cancer types and promotes cancer progression, metastasis, and CSCs survival ( Arnouk et al, 2021 ). Besides, as reviewed by Tsai et al (2021) , Cripto-1 promoted EMT in mouse mammary tumours, which can be associated with EMT gene expression of CSCs to promote their self-renewal, invasion, and metastasis.…”

Section: Breast Cancer Stem Cells (Bcscs)mentioning

confidence: 99%

Therapy-resistant breast cancer in focus: Clinically relevant mitigation by flavonoids targeting cancer stem cells

et al. 2023

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Significant limitations of the reactive medical approach in breast cancer management are clearly reflected by alarming statistics recorded worldwide. According to the WHO updates, breast malignancies become the leading cancer type. Further, the portion of premenopausal breast cancer cases is permanently increasing and demonstrates particularly aggressive patterns and poor outcomes exemplified by young patients with triple-negative breast cancer that lacks targeted therapy. Accumulating studies suggest the crucial role of stem cells in tumour biology, high metastatic activity, and therapy resistance of aggressive breast cancer. Therefore, targeting breast cancer stem cells is a promising treatment approach in secondary and tertiary breast cancer care. To this end, naturally occurring substances demonstrate high potential to target cancer stem cells which, however, require in-depth analysis to identify effective anti-cancer agents for cost-effective breast cancer management. The current article highlights the properties of flavonoids particularly relevant for targeting breast cancer stem cells to mitigate therapy resistance. The proposed approach is conformed with the principles of 3P medicine by applying predictive diagnostics, patient stratification and treatments tailored to the individualised patient profile. Expected impacts are very high, namely, to overcome limitations of reactive medical services improving individual outcomes and the healthcare economy in breast cancer management. Relevant clinical applications are exemplified in the paper.

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“…The Wnt/β-catenin signaling is strictly regulated in normal cells; however, it has been dysregulated in various cancers including prostate cancer [58,59]. One of the EMT-promoting factor Cripto-1 (CR-1), a member of epidermal growth factor family, is upregulated in metastatic prostate cancers and is associated with decreased membrane associated β-catenin and increased nuclear β-catenin [110,111] and knocking down its expression inhibits cell proliferation, migration, and invasion [112]. CR-1 has a central role in regulating and cross-talking with various cellular signaling mechanisms including TGF-β, MAPK, and Wnt/β-catenin [113].…”

Section: Adt In the Treatment Of Advanced Pcamentioning

confidence: 99%

Dissecting the effects of androgen deprivation therapy on cadherin switching in advanced prostate cancer: A molecular perspective

Varisli¹,

TOLAN²,

CEN³

et al. 2022

Oncology Research

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Prostate cancer is one of the most often diagnosed malignancies in males and its prevalence is rising in both developed and developing countries. Androgen deprivation therapy has been used as a standard treatment approach for advanced prostate cancer for more than 80 years. The primary aim of androgen deprivation therapy is to decrease circulatory androgen and block androgen signaling. Although a partly remediation is accomplished at the beginning of treatment, some cell populations become refractory to androgen deprivation therapy and continue to metastasize.Recent evidences suggest that androgen deprivation therapy may cause cadherin switching, from E-cadherin to Ncadherin, which is the hallmark of epithelial-mesenchymal transition. Diverse direct and indirect mechanisms are involved in this switching and consequently, the cadherin pool changes from E-cadherin to N-cadherin in the epithelial cells. Since E-cadherin represses invasive and migrative behaviors of the tumor cells, the loss of E-cadherin disrupts epithelial tissue structure leading to the release of tumor cells into surrounding tissues and circulation. In this study, we review the androgen deprivation therapy-dependent cadherin switching in advanced prostate cancer with emphasis on its molecular basis especially the transcriptional factors regulated through TFG-β pathway.

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Cripto-1 as a Key Factor in Tumor Progression, Epithelial to Mesenchymal Transition and Cancer Stem Cells

Cited by 9 publications

References 70 publications

CRIPTO Is a Marker of Chemotherapy-Induced Stem Cell Expansion in Non-Small Cell Lung Cancer

CRIPTO Is a Marker of Chemotherapy-Induced Stem Cell Expansion in Non-Small Cell Lung Cancer

Therapy-resistant breast cancer in focus: Clinically relevant mitigation by flavonoids targeting cancer stem cells

Dissecting the effects of androgen deprivation therapy on cadherin switching in advanced prostate cancer: A molecular perspective

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