DAP1 high expression increases risk of lymph node metastases in squamous cell carcinoma of the oral cavity

Santos, Marcelo dos; Maia, L.L.; Silva, C.V.M.; Peterle, Gabriela Tonini; Mercante, A.M.C.; Nunes, Fábio Daumas; Carvalho, Marcos Brasilino de; Tajara, Eloíza H.; Louro, Iúri Drumond; Silva, Adriana Madeira Álvares da

doi:10.4238/2015.september.8.13

Cited by 5 publications

(7 citation statements)

References 25 publications

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“…Surprisingly, WM266-4 but not WM115 cells were shown to carry high levels of the DAP /DAP1 proteomic component (96.65) ( Table S3 ), a small, proline-rich, cytoplasmic protein, which belongs to the death-associated protein family [ 89 , 90 ]. Activated (de-phosphorylated) DAP1 negatively regulates autophagy, while its elevated expression increases the risk of lymph-node metastasis in squamous cell carcinoma of the oral cavity [ 91 , 92 , 93 ]. Thereby, DAP1 could be endowed with a property to promote melanoma advancement from primary (e.g., WM115) to the metastatic (e.g., WM266-4) stage by downregulating the autophagic machinery whose functionality may differ between WM266-4 [ 35 ] and WM115 cells ( Figure 1 C; n = 47) (see also Figure 8G).…”

Section: Resultsmentioning

confidence: 99%

From Proteomic Mapping to Invasion-Metastasis-Cascade Systemic Biomarkering and Targeted Drugging of Mutant BRAF-Dependent Human Cutaneous Melanomagenesis

Giannopoulou

Velentzas

Anagnostopoulos

et al. 2021

Cancers

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Melanoma is classified among the most notoriously aggressive human cancers. Despite the recent progress, due to its propensity for metastasis and resistance to therapy, novel biomarkers and oncogenic molecular drivers need to be promptly identified for metastatic melanoma. Hence, by employing nano liquid chromatography-tandem mass spectrometry deep proteomics technology, advanced bioinformatics algorithms, immunofluorescence, western blotting, wound healing protocols, molecular modeling programs, and MTT assays, we comparatively examined the respective proteomic contents of WM115 primary (n = 3955 proteins) and WM266-4 metastatic (n = 6681 proteins) melanoma cells. It proved that WM115 and WM266-4 cells have engaged hybrid epithelial-to-mesenchymal transition/mesenchymal-to-epithelial transition states, with TGF-β controlling their motility in vitro. They are characterized by different signatures of SOX-dependent neural crest-like stemness and distinct architectures of the cytoskeleton network. Multiple signaling pathways have already been activated from the primary melanoma stage, whereas HIF1α, the major hypoxia-inducible factor, can be exclusively observed in metastatic melanoma cells. Invasion-metastasis cascade-specific sub-routines of activated Caspase-3-triggered apoptosis and LC3B-II-dependent constitutive autophagy were also unveiled. Importantly, WM115 and WM266-4 cells exhibited diverse drug response profiles, with epirubicin holding considerable promise as a beneficial drug for metastatic melanoma clinical management. It is the proteome navigation that enables systemic biomarkering and targeted drugging to open new therapeutic windows for advanced disease.

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Section: Resultsmentioning

confidence: 99%

From Proteomic Mapping to Invasion-Metastasis-Cascade Systemic Biomarkering and Targeted Drugging of Mutant BRAF-Dependent Human Cutaneous Melanomagenesis

Giannopoulou

Velentzas

Anagnostopoulos

et al. 2021

Cancers

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“…Indeed, bioinformatics analysis demonstrated that a low level of DAP1 was associated with a longer time to overall survival in ovarian cancer patients. It is reported that a high expression of DAP1 increased the risk of lymph node metastasis in oral squamous cell carcinoma (Santos et al, 2015). In contrast, it is demonstrated that DAP1 silencing increased cell adhesion and migration of human breast cancer cells (Wazir et al, 2015; Wazir, Jiang, Sharma, & Mokbel, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…However, the biological functions of DAP1 are controversial. Either promotion or inhibition of DAP1 has been reported to promote or inhibit the growth of a variety of tumors (Jia et al, 2014; Santos et al, 2015). However, the specific expression and biological roles of DAP1 in ovarian cancer are still unclear.…”

Section: Introductionmentioning

confidence: 99%

DAP1 negatively regulates autophagy induced by cardamonin in SKOV3 cells

Nie

Chen

Niu

et al. 2020

Cell Biology International

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Autophagy is closely related to the formation and development of multiple human tumors including ovarian cancer. As a major regulator of this process, the role of mTOR (mammalian target of rapamycin) has been well proven. Cardamonin, a kind of flavonoid from plants, has effects on induction of autophagy and thus antiproliferation of cancer cells. However, the detailed mechanism remains unclear. DAP1 (death-associated protein 1) is a proline-rich protein, which is involved in the regulation of cellular growth and programmed cell death including autophagy and apoptosis. The aim of this study was to investigate whether DAP1 is involved in proliferation inhibition and autophagy induced by cardamonin in tumor cells. Using online bioinformatics tools, we found that DAP1 expression is closely related to the survival of patients with ovarian cancer. Our study showed that autophagy induced by cardamonin was associated with mTOR inhibition, and DAP1 was involved in this process. Silence of DAP1 decreased cell proliferation but enhanced the antiproliferative effect of cardamonin in SKOV3 cells. The level of autophagy was elevated by DAP1 silencing in SKOV3 cells. Notably, cardamonin showed higher autophagy flux in the DAP1 small interfering RNA group. Taken together, our results implied that DAP1 negatively regulates autophagy induced by cardamonin, and it may be a potential target for ovarian cancer therapy.

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“…In this context a connection between DAP1, autophagocytosis and human carcinogenesis has been discovered (Wazir et al 2015). The presence of DAP1 is associated to a favorable prognosis in breast, ovarian, colorectal cancer and others (Wazir et al 2015;Nie et al 2020;Jia et al 2014), even though the positive influence is still under discussion in the literature (Santos et al 2015).…”

Section: Biological Contextmentioning

confidence: 99%

Backbone and nearly complete side-chain chemical shift assignments of the human death-associated protein 1 (DAP1)

et al. 2020

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Death-associated protein 1 (DAP1) is a proline-rich cytoplasmatic protein highly conserved in most eukaryotes. It has been reported to be involved in controlling cell growth and migration, autophagy and apoptosis. The presence of human DAP1 is associated to a favourable prognosis in different types of cancer. Here we describe the almost complete $${{^{1}}\text {H}}$$ 1 H , $${{^{13}}\text {C}}$$ 13 C , and $${{^{15}}\text {N}}$$ 15 N chemical shift assignments of the human DAP1. The limited spectral dispersion, mainly in the $${{^{1}}\text {H}{^{\text{N}}}}$$ 1 H N region, and the lack of defined secondary structure elements, predicted based on chemical shifts, identifies human DAP1 as an intrinsically disordered protein (IDP). This work lays the foundation for further structural investigations, dynamic studies, mapping of potential interaction partners or drug screening and development.

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DAP1 high expression increases risk of lymph node metastases in squamous cell carcinoma of the oral cavity

Cited by 5 publications

References 25 publications

From Proteomic Mapping to Invasion-Metastasis-Cascade Systemic Biomarkering and Targeted Drugging of Mutant BRAF-Dependent Human Cutaneous Melanomagenesis

From Proteomic Mapping to Invasion-Metastasis-Cascade Systemic Biomarkering and Targeted Drugging of Mutant BRAF-Dependent Human Cutaneous Melanomagenesis

DAP1 negatively regulates autophagy induced by cardamonin in SKOV3 cells

Backbone and nearly complete side-chain chemical shift assignments of the human death-associated protein 1 (DAP1)

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