Emerging roles of plasma gelsolin in tumorigenesis and modulating the tumor microenvironment

Hsieh, Chih‐Hsiung; Wang, Yi‐Ching

doi:10.1002/kjm2.12578

Cited by 8 publications

(10 citation statements)

References 65 publications

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“…2 a) 33 , gelsolin (GSN, Fig. 2 b) 34 , chemokine (C–C motif) ligand 5 (CCL5, Fig. 2 b) 35 , 36 , galectin-3 (LGALS3, Fig.…”

Section: Resultsmentioning

confidence: 99%

Mitofusin 1 silencing decreases the senescent associated secretory phenotype, promotes immune cell recruitment and delays melanoma tumor growth after chemotherapy

Tarallo,

Martínez,

Leyva

et al. 2024

Sci Rep

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Cellular senescence is a therapy endpoint in melanoma, and the senescence-associated secretory phenotype (SASP) can affect tumor growth and microenvironment, influencing treatment outcomes. Metabolic interventions can modulate the SASP, and mitochondrial energy metabolism supports resistance to therapy in melanoma. In a previous report we showed that senescence, induced by the DNA methylating agent temozolomide, increased the level of fusion proteins mitofusin 1 and 2 in melanoma, and silencing Mfn1 or Mfn2 expression reduced interleukin-6 secretion by senescent cells. Here we expanded these observations evaluating the secretome of senescent melanoma cells using shotgun proteomics, and explored the impact of silencing Mfn1 on the SASP. A significant increase in proteins reported to reduce the immune response towards the tumor was found in the media of senescent cells. The secretion of several of these immunomodulatory proteins was affected by Mfn1 silencing, among them was galectin-9. In agreement, tumors lacking mitofusin 1 responded better to treatment with the methylating agent dacarbazine, tumor size was reduced and a higher immune cell infiltration was detected in the tumor. Our results highlight mitochondrial dynamic proteins as potential pharmacological targets to modulate the SASP in the context of melanoma treatment.

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“…2 a) 33 , gelsolin (GSN, Fig. 2 b) 34 , chemokine (C–C motif) ligand 5 (CCL5, Fig. 2 b) 35 , 36 , galectin-3 (LGALS3, Fig.…”

Section: Resultsmentioning

confidence: 99%

Mitofusin 1 silencing decreases the senescent associated secretory phenotype, promotes immune cell recruitment and delays melanoma tumor growth after chemotherapy

Tarallo,

Martínez,

Leyva

et al. 2024

Sci Rep

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“…Gelsolin is an actin binding and calcium regulated protein which is involved in assembly and disassembly of actin filaments influencing cell morphology, differentiation, movement, and apoptosis (43)(44)(45). The GSN gene has many alternative splicing transcripts but in the main encodes two gelsolin isoforms: a 731 amino acid long/80 kDa cytosolic protein (NP_001121134.1) and a plasma 782 amino acid long/86 kDa in weight protein (NP_000168.1) found in the plasma of humans (46)(47)(48).…”

Section: Discussionmentioning

confidence: 99%

“…The GSN gene has many alternative splicing transcripts but in the main encodes two gelsolin isoforms: a 731 amino acid long/80 kDa cytosolic protein (NP_001121134.1) and a plasma 782 amino acid long/86 kDa in weight protein (NP_000168.1) found in the plasma of humans (46)(47)(48). Plasma gelsolin has a signal peptide not found in the cytosolic form of the protein (43)(44)(45)(46)(47)(48). Depending on the type of neoplasm, gelsolin has been reported to have tumor suppression or oncogenetic function (44,45).…”

Section: Discussionmentioning

confidence: 99%

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Fusion of the High-mobility Group AT-Hook 2 (HMGA2) and the Gelsolin (GSN) Genes in Lipomas With t(9;12)(q33;q14) Chromosomal Translocation

Panagopoulos

Andersen

Brunetti

et al. 2023

In Vivo

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Background/Aim: Lipomas are benign tumors composed of mature fat cells. They are common soft tissue tumors that often carry chromosome aberrations involving 12q14 resulting in rearrangements, deregulation, and generation of chimeras of the high-mobility group AT-hook 2 gene (HMGA2) which maps in 12q14.3. In the present study, we report the finding of t(9;12)(q33;q14) translocation in lipomas and describe its molecular consequences. Materials and Methods: Four lipomas from two male and two female adult patients were selected because their neoplastic cells carried a t(9;12)(q33;q14) as the sole karyotypic aberration. The tumors were investigated using RNA sequencing, reverse transcription polymerase chain reaction (RT-PCR), and Sanger sequencing techniques. Results: RNA sequencing of a t(9;12)(q33;q14)-lipoma detected an in-frame fusion of HMGA2 with the gelsolin gene (GSN) from 9q33. RT-PCR together with Sanger sequencing confirmed the presence of an HMGA2::GSN chimera in the tumor as well as in two other tumors from which RNA was available. The chimera was predicted to code for an HMGA2::GSN protein which would contain the three AT-hook domains of HMGA2 and the

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“…GSN is ubiquitously expressed in different cell types and functions as a multifunctional regulator of cell [ 14 ]. Here, we focused on its impacts on HCC metastasis.…”

Section: Discussionmentioning

confidence: 99%

GSN synergies with actin-related transfer molecular chain to promote invasion and metastasis of HCC

Zhou

2022

Clin Transl Oncol

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Background Previous studies have shown that the ability of tumor cells to move and migrate is related to the molecular chain pathway mediated by actin. This study focused on the molecular mechanism of gelsolin (GSN) as an important actin-binding protein in promoting HCC invasion and metastasis. Methods The relationship between GSN expression and clinical characteristics was observed by immunohistochemistry (IHC). In vitro and in vivo experiments confirmed the role of GSN in HCC metastasis. Dual-immunoprecipitation (IP), immunofluorescence (IF), western blotting, and the gelatinase activity assay were used to investigate the mechanism of GSN-promoting metastasis. PEX fusion proteins were used to intervene in the transfer molecular chain. Results Our study found that GSN promoted HCC invasion and metastasis through its synergistic effect with actin-related transfer molecular chain (actin-CD44-MMPs). Concretely, as an important binding molecule of actin, GSN activated MMP2 by interacting with MMP14. Furthermore, CD44 might be a key node in the above-mentioned mechanism. The use of MMP14 domain (PEX fusion protein) to competitively bind to CD44 helped to inhibit the activation of downstream MMP2. Conclusions GSN played crucial roles in HCC metastatic process. An improved understanding of the multiple effects of GSN in HCC might facilitate a deeper appreciation of GSN as an important HCC regulator. The study identified GSN and its regulated transfer molecular chain as potential therapeutic targets for HCC.

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Emerging roles of plasma gelsolin in tumorigenesis and modulating the tumor microenvironment

Cited by 8 publications

References 65 publications

Mitofusin 1 silencing decreases the senescent associated secretory phenotype, promotes immune cell recruitment and delays melanoma tumor growth after chemotherapy

Mitofusin 1 silencing decreases the senescent associated secretory phenotype, promotes immune cell recruitment and delays melanoma tumor growth after chemotherapy

Fusion of the High-mobility Group AT-Hook 2 (HMGA2) and the Gelsolin (GSN) Genes in Lipomas With t(9;12)(q33;q14) Chromosomal Translocation

GSN synergies with actin-related transfer molecular chain to promote invasion and metastasis of HCC

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