SEC23A Inhibit Melanoma Metastatic through Secretory PF4 Cooperation with SPARC to Inhibit MAPK Signaling Pathway

Zeng, Bin; Sun, Zhiwei; Zhao, Qiting; Liu, Doudou; Chen, Hao; Li, Xiaoshuang; Xing, H. Rosie; Wang, Yunlong

doi:10.7150/ijbs.60866

Cited by 8 publications

(8 citation statements)

References 32 publications

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“…Next, we examined whether POL cells can augment the metastatic competency of OL cells via the secretory protein pathway. We have shown previously that Sec23a inhibits metastatic colonization efficiency of melanoma by regulating the transportation of secretory proteins [14,24]. In this study, we first measured whether Sec23a mRNA and protein expression in OL cells were altered upon co‐culture with POL cells.…”

Section: Resultsmentioning

confidence: 99%

“…Fourthly, we prioritized S100A11 from 198 secretory proteins of POL and made the prediction that POL‐secreted S100A11 inhibits Sec23a in OL cells. Our previous studies have shown that Sec23a inhibits metastatic colonization by regulation of the secretome [14,24]. Thus, Sec23a is the initiator of the tumor‐suppressive activity of the Sec23a‐dependent secretome.…”

Section: Discussionmentioning

confidence: 99%

“…4Aa-b). Since the co-culture of OL cells with POL cells leads to Sec23a inhibition in OL cells, and Sec23a is antimetastatic in our prior characterization [14,24], Sec23a-dependent secretome was profiled by the protein mass spectrometry. We identified 28 downregulated secretory proteins in the conditioned medium of OL-shSec23a cells in which Sec23a was silenced compared with that of OL cells (Fig.…”

Section: Prioritization and Validation Of Common Mediators Of Mirna-4...mentioning

confidence: 99%

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Synergistic inhibition of NUDT21 by secretory S100A11 and exosomal miR‐487a‐5p promotes melanoma oligo‐ to poly‐metastatic progression

Zeng

Chen

et al. 2023

Molecular Oncology

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Although early diagnosis and therapeutic advances have transformed the living quality and outcome of cancer patients, the poor prognosis for metastatic patients has not been significantly improved. Mechanisms underlying the complexity of metastasis cannot be simply determined by the straightforward ‘cause‐and‐effect relationships’. We have developed a ‘dry‐lab‐driven knowledge discovery and wet‐lab validation’ approach to embrace the complexity of cancer and metastasis. We have revealed for the first time that polymetastatic (POL) melanoma cells can utilize both the secretory protein pathway (S100A11–Sec23a) and the exosomal crosstalk (miR‐487a‐5p) to transfer their ‘polymetastatic competency’ to the oligometastatic (OL) melanoma cells, via synergistic co‐targeting of the tumor‐suppressor Nudt21. The downstream deregulated glycolysis was verified to regulate metastatic colonization efficiency. Further, two gene sets conferring independent prognosis in melanoma were identified, which have the potential for clinical translation and merit future clinical validation.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Prioritization and Validation Of Common Mediators Of Mirna-4...mentioning

confidence: 99%

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Synergistic inhibition of NUDT21 by secretory S100A11 and exosomal miR‐487a‐5p promotes melanoma oligo‐ to poly‐metastatic progression

Zeng

Chen

et al. 2023

Molecular Oncology

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“…In our previous study, we discovered that secretory proteins in the paracrine pathway can mediate the communications between tumor cells with different metastatic ability [ 36 ]. Exosomes, a new category of paracrine substances, have more complex contents and higher delivery efficiency [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Exosomal lncRNA Mir100hg derived from cancer stem cells enhance glycolysis and promote metastasis of lung adenocarcinoma through mircroRNA-15a-5p/31-5p

Shi,

Li,

Zhang

et al. 2023

Cell Commun Signal

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Background Exosomes are a new class of molecular entities in the metastatic microenvironment, which can mediate bidirectional communication between cells. While exosomes-mediated interactions between tumor cells and other cell populations in the tumor microenvironment have attracted most attention, little is known about the significance of exosomes in mediating the interaction between non-stemness cancer cells and cancer stem cells during cancer progression. Methods The structure, sequence and downstream target miRNAs of lncRNA Mir100hg were predicted by online web resources. The bioinformatics prediction results were validated with experimental verification: exosome tracing, electron microscopy, Luciferase assay, metabolomics sequencing and mouse tail vein model of pulmonary metastasis. A complex regulatory network of "cancer stem cells-exosomal lncRNA-non-stem cancer cells" was constructed. Results This study demonstrates firstly that lncRNA Mir100hg is upregulated in lung cancer stem cell LLC-SD (Lung cancer stem cells) and can be delivered to non-stemness cancer cells LLC (Lewis lung cancer cells) via exosomes. In LLC, Mir100hg targets miR-15a-5p and miR-31-5p which leads to the increase of the global glycolytic activity of lung cancer cells and consequently, the enhancement of their metastatic capability. Conclusion We delineated a complex regulatory network that utilized by cancer stem cells to transfer their high metastatic activity to the low-metastatic non-stemness cancer cells through exosomal Mir100hg, thereby providing new mechanistic insights into the communication between two heterogeneous tumor cells.

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“…Additionally, the available information on PF4 expression in tumor cells is still limited and may vary depending on the specific type of cancer. For example, in oligometastatic melanoma cells, Pf4 knockout increases cell migration in vitro and lung metastasis formation in vivo 64 . Similarly, in human head and neck cancer tumor cells, Pf4 overexpression reduces tumor growth and increases survival 65 .…”

Section: Discussionmentioning

confidence: 99%

Aerobic exercise training mitigates tumor growth and cancer-induced splenomegaly through modulation of non-platelet platelet factor 4 expression

Tobias,

Gomes,

Fernandes

et al. 2023

Sci Rep

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Exercise training reduces the incidence of several cancers, but the mechanisms underlying these effects are not fully understood. Exercise training can affect the spleen function, which controls the hematopoiesis and immune response. Analyzing different cancer models, we identified that 4T1, LLC, and CT26 tumor-bearing mice displayed enlarged spleen (splenomegaly), and exercise training reduced spleen mass toward control levels in two of these models (LLC and CT26). Exercise training also slowed tumor growth in melanoma B16F10, colon tumor 26 (CT26), and Lewis lung carcinoma (LLC) tumor-bearing mice, with minor effects in mammary carcinoma 4T1, MDA-MB-231, and MMTV-PyMT mice. In silico analyses using transcriptome profiles derived from these models revealed that platelet factor 4 (Pf4) is one of the main upregulated genes associated with splenomegaly during cancer progression. To understand whether exercise training would modulate the expression of these genes in the tumor and spleen, we investigated particularly the CT26 model, which displayed splenomegaly and had a clear response to the exercise training effects. RT-qPCR analysis confirmed that trained CT26 tumor-bearing mice had decreased Pf4 mRNA levels in both the tumor and spleen when compared to untrained CT26 tumor-bearing mice. Furthermore, exercise training specifically decreased Pf4 mRNA levels in the CT26 tumor cells. Aspirin treatment did not change tumor growth, splenomegaly, and tumor Pf4 mRNA levels, confirming that exercise decreased non-platelet Pf4 mRNA levels. Finally, tumor Pf4 mRNA levels are deregulated in The Cancer Genome Atlas Program (TCGA) samples and predict survival in multiple cancer types. This highlights the potential therapeutic value of exercise as a complementary approach to cancer treatment and underscores the importance of understanding the exercise-induced transcriptional changes in the spleen for the development of novel cancer therapies.

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SEC23A Inhibit Melanoma Metastatic through Secretory PF4 Cooperation with SPARC to Inhibit MAPK Signaling Pathway

Cited by 8 publications

References 32 publications

Synergistic inhibition of NUDT21 by secretory S100A11 and exosomal miR‐487a‐5p promotes melanoma oligo‐ to poly‐metastatic progression

Synergistic inhibition of NUDT21 by secretory S100A11 and exosomal miR‐487a‐5p promotes melanoma oligo‐ to poly‐metastatic progression

Exosomal lncRNA Mir100hg derived from cancer stem cells enhance glycolysis and promote metastasis of lung adenocarcinoma through mircroRNA-15a-5p/31-5p

Aerobic exercise training mitigates tumor growth and cancer-induced splenomegaly through modulation of non-platelet platelet factor 4 expression

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