The p53 status can influence the role of Sam68 in tumorigenesis

Li, Naomi; Ngo, Chau Tuan-Anh; Aleynikova, Olga; Beauchemin, Nicole; Richard, Stéphane

doi:10.18632/oncotarget.12305

Cited by 7 publications

(1 citation statement)

References 66 publications

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“…Since its original identification as the first mitotic substrate and binding partner of Src tyrosine kinase, Sam68 has been reported to fulfill versatile functions in an array of important cellular processes including RNA metabolism, adipogenesis, gametogenesis, transcription, and others . More importantly, an increasing number of studies support an emerging role of Sam68 in tumor progression and development ; in particular, we recently uncovered that Sam68 is a key regulator of the DNA damage sensor PARP1 and plays an indispensable role in the very early cellular signaling cascade in response to DNA damage . Herein, we report that Sam68 regulates DNA damage‐initiated DNA repair and NF‐κB signaling pathways in keratinocytes and that Sam68 is crucial for the growth and survival of skin tumors in mice, which suggests a novel role of Sam68 in the development of NMSC and lends additional support to the pro‐oncogenic properties of Sam68.…”

Section: Discussionmentioning

confidence: 61%

Sam68 is required for the growth and survival of nonmelanoma skin cancer

Sun

Xia

et al. 2019

Cancer Medicine

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Although targeting DNA repair signaling pathways has emerged as a promising therapeutic for skin cancer, the relevance of DNA damage responses (DDR) in the development and survival of nonmelanoma skin cancer (NMSC), the most common type of skin cancer, remains obscure. Here, we report that Src‐associated substrate during mitosis of 68 kDa (Sam68), an early signaling molecule in DDR, is elevated in skin tumor tissues derived from NMSC patients and skin lesions from Gli2‐transgenic mice. Downregulation of Sam68 impacts the growth and survival of human tumor keratinocytes and genetic ablation of Sam68 delays the onset of basal cell carcinomas (BCC) in Gli2‐transgenic mice. Moreover, Sam68 plays a critical role in DNA damage‐induced DNA repair and nuclear factor kappa B (NF‐κB) signaling pathways in keratinocytes, hence conferring keratinocyte sensitivity to DNA damaging agents. Together, our data reveal a novel function of Sam68 in regulating DDR in keratinocytes that is crucial for the growth and survival of NMSC.

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Section: Discussionmentioning

confidence: 61%

Sam68 is required for the growth and survival of nonmelanoma skin cancer

Sun

Xia

et al. 2019

Cancer Medicine

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Sam68 Allows Selective Targeting of Human Cancer Stem Cells

Benoit

Mitchell

Risueño

et al. 2017

Cell Chemical Biology

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Targeting of human cancer stem cells (CSCs) requires the identification of vulnerabilities unique to CSCs versus healthy resident stem cells (SCs). Unfortunately, dysregulated pathways that support transformed CSCs, such as Wnt/β-catenin signaling, are also critical regulators of healthy SCs. Using the ICG-001 and CWP family of small molecules, we reveal Sam68 as a previously unappreciated modulator of Wnt/β-catenin signaling within CSCs. Disruption of CBP-β-catenin interaction via ICG-001/CWP induces the formation of a Sam68-CBP complex in CSCs that alters Wnt signaling toward apoptosis and differentiation induction. Our study identifies Sam68 as a regulator of human CSC vulnerability.

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Publisher Note

Zhang

2017

Journal of Molecular Graphics and Modelling

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Human sacum is regulatory adaptor protein involved in cellular signaling network of colorectal cancer. Molecular evidence suggests that the protein is integrated into oncogenic signaling network by binding to SH3-containing proteins through its proline-rich motifs. In this study, we have performed a transcriptome-wide analysis and identification of sacum-binding partners in the genome profile of human colorectal cancer. The sacum-binding potency of SH3-containing proteins found in colorectal cancer was investigated by using bioinformatics modeling and intermolecular binding analysis. With the protocol we were able to predict those high-affinity domain binders of the proline-rich peptides of human sacum in a high-throughput manner, and to analyze sequence-specific interaction in the domain-peptide recognition at molecular level. Consequently, a number of putative domain binders with both high affinity and specificity were identified, from which the Src SH3 domain was selected as a case study and tested for its binding activity towards the sacum peptides. We also designed two peptide variants that may have potent capability to competitively disrupt sacum interaction with its partners.

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The p53 status can influence the role of Sam68 in tumorigenesis

Cited by 7 publications

References 66 publications

Sam68 is required for the growth and survival of nonmelanoma skin cancer

Sam68 is required for the growth and survival of nonmelanoma skin cancer

Sam68 Allows Selective Targeting of Human Cancer Stem Cells

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