Formin-like 1 (FMNL1) Is Associated with Glioblastoma Multiforme Mesenchymal Subtype and Independently Predicts Poor Prognosis

Higa, Nayuta; Shinsato, Yoshinari; Kamil, Muhammad; Hirano, Takuro; Takajo, Tomoko; Shimokawa, Masahiro; Minami, Kentaro; Yamamoto, Masayuki; Kawahara, Kohichi; Yonezawa, Hajime; Hirano, Hirofumi; Furukawa, Tatsuhiko; Yoshimoto, Koji; Arita, Kazunori

doi:10.3390/ijms20246355

Cited by 14 publications

(14 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, high FMNL1 expression was correlated with poor overall and disease-free survivals. Our data were consistent with previous studies reporting FMNL1 was overexpressed in glioblastoma, lung cancer and nasopharyngeal carcinoma, and was associated with patient prognosis (9)(10)(11). According to TCGA data, gene amplification of FMNL1 was rare in ccRCC cells, and is insufficient to support the high expression of FMNL1.…”

Section: Discussionsupporting

confidence: 90%

“…A growing body of evidence showed that FMNL1 was overexpressed in acute lymphoblastic, myeloid, promyelocytic leukemia, and chronic myelogenous leukemia to promote the pathogenic progression (6)(7)(8). Strikingly, FMNL1 was also found to be upregulated in solid tumors, such as nasopharyngeal carcinoma (9), non-small cell lung cancer (10), and gioblastoma (11). Functionally, FMNL1 was able to activate the epithelial to mesenchymal transition (EMT) to promote tumor progression (9,10).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

FMNL1 Exhibits Pro-Metastatic Activity via CXCR2 in Clear Cell Renal Cell Carcinoma

Zhang

Yang

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

Formin-like (FMNL) proteins are responsible for cytoskeletal remodeling and have been implicated in the progression and spread of human cancers. Yet the clinical significance and biological function of FMNL1 in clear cell renal cell carcinoma (ccRCC) remain unclear. In this study, the expression of FMNL1 in ccRCC and its clinical value were determined by tissue microarray-based IHC and statistical analyses. The role of FMNL1 in ccRCC metastasis and the underlying mechanism were investigated via in vitro and in vivo models using gene regulation detection, ChIP, Luciferase reporter assays, and rescue experiments. We show that FMNL1 is upregulated in ccRCC and exhibits pro-metastatic activity via induction of CXCR2. High expression of FMNL1 is significantly correlated with advanced tumor stage, higher pathological tumor grade, tumor metastasis, and unfavorable prognosis in two independent cohorts containing over 800 patients with ccRCC. The upregulation of FMNL1 in ccRCC is mediated by the loss of GATA3. Ectopic expression of FMNL1 promotes, whereas FMNL1 depletion inhibits cell migration in vitro and tumor metastasis in vivo. The FMNL1-enhanced cell mobility is markedly attenuated by the knockdown of CXCR2. Further studies demonstrate that FMNL1 increases the expression of CXCR2 via HDAC1. In clinical samples, FMNL1 expression is positively associated with CXCR2, and is negatively connected to GATA3 expression. Collectively, our data suggest FMNL1 serve as a potential prognostic factor and function as an oncogene. The axis of GATA3/FMNL1/CXCR2 may present a promising therapeutic target for tumor metastasis in ccRCC.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

FMNL1 Exhibits Pro-Metastatic Activity via CXCR2 in Clear Cell Renal Cell Carcinoma

Zhang

Yang

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…These results indicate that FMNL1 may have a role in GC tumor progression. A similar association has been seen in other cancers [8,27].…”

Section: Discussionsupporting

confidence: 85%

FHOD1 and FMNL1 formin proteins in intestinal gastric cancer: correlation with tumor-infiltrating T lymphocytes and molecular subtypes

et al. 2021

View full text Add to dashboard Cite

Background Gastric cancer (GC) is the third most common cause of cancer death. Intestinal type GC is a molecularly diverse disease. Formins control cytoskeletal processes and have been implicated in the progression of many cancers. Their clinical significance in GC remains unclear. Here, we characterize the expression of formin proteins FHOD1 and FMNL1 in intestinal GC tissue samples and investigate their association with clinical parameters, GC molecular subtypes and intratumoral T lymphocytes. Methods The prognostic significance of FHOD1 and FMNL1 mRNA expression was studied with Kaplan–Meier analyses in an online database. The expression of FHOD1 and FMNL1 proteins was characterized in GC cells, and in non-neoplastic and malignant tissues utilizing tumor microarrays of intestinal GC representing different molecular subtypes. FHOD1 and FMNL1 expression was correlated with clinical parameters, molecular features and T lymphocyte infiltration. Immunohistochemical expression of neither formin correlated with survival. Results Kaplan–Meier analysis associated high FHOD1 and FMNL1 mRNA expression with reduced overall survival (OS). Characterization of FHOD1 and FMNL1 in GC cells showed cytoplasmic expression along the actin filaments. Similar pattern was recapitulated in GC tissue samples. Elevated FMNL1 was associated with larger tumor size and higher disease stage. Downregulation of FHOD1 associated with TP53-mutated GC tumors. Tumor cell FHOD1 expression strongly correlated with high numbers of tumor-infiltrating CD8 + lymphocytes. Conclusions FHOD1 and FMNL1 proteins are expressed in the tumor cells of intestinal GC and significantly associate with clinical parameters without direct prognostic significance. FHOD1 correlates with high intratumoral CD8 + T lymphocyte infiltration in this cohort.

show abstract

“…FMNL1 belongs to a member of formin family of proteins and have been implicated in the regulation of cell morphology, cytoskeletal organization and cell migration [18]. As reported before, FMNL1 was upregulated in various malignancies, like lymphoma, T non-Hodgkin's lymphomas, GBM (Glioblastoma multiforme), NSCLC and NPC [19,20,21]. Involvement of FMNL1 in the physiological mechanism of malignancies has been reported.…”

Section: Discussionmentioning

confidence: 65%

Quantitative proteomic analysis reveals sophisticated metabolic alteration and identifies FMNL1 as a prognostic marker in clear cell renal cell carcinoma

Ma¹,

Wang²,

Liu³

et al. 2021

J. Cancer

View full text Add to dashboard Cite

In this study, we have undertaken the whole proteomic analysis and got a better understanding of biological processes involved in the development and progression of ccRCC. We hope promising biomarkers can be uncovered to facilitate early diagnosis, predict the prognosis and progression, more importantly, to be applied as potential therapeutic targets. Experimental design: Fresh frozen tissue samples were surgically resected from patients with local or locally advanced ccRCC. Trypsin digested proteins were analyzed using TMT-based LC-MS/MS proteomic approach, followed by bioinformatic analysis. A potential prognostic marker FMNL1 was chosen to be validated in TCGA_KIRC datasets (n=525 and 72), further validation sets (n=10 and 10) and expanded validation sets (n=81 and 16). The effects of FMNL1 on proliferation, migration and invasion were determined by colony formation, wound healing, and transwell assays in 786-O and Caki-1 cells in vitro study. Results: A total of 657 differentially expressed proteins were identified and quantified between ccRCC and adjacent normal tissues (p-value<0.05, FC>2 or<1/2), of which 186 proteins were up-regulated and 471 proteins were down-regulated. Bioinformatic analysis showed enriched metabolic biological processes and pathways. Univariate and multivariate analysis defined FMNL1 as an independent negative prognostic marker in the TCGA datasets. High expression of FMNL1 correlated significantly with tumor stage and distant metastasis (P<0.05) both in the TCGA-KIRC datasets and expanded validation sets. Kaplan-Meier survival curve illustrated that the patients with high FMNL1 protein level had shorter OS time in the expanded validation sets (p=0.0273). In vitro experiments presented the functional effects of FMNL1 knockdown on the inhibition of proliferation, migration and invasion in cancer cell lines. Conclusion and clinical relevance:The proteomic results uncovered sophisticated metabolic reprogramming of ccRCC and indicated that the upregulation of rate-limiting enzymes in glycolysis and mitochondrial impairment may be the cause of metabolic reprogramming in ccRCC. Moreover, FMNL1 has been identified as a promising prognostic marker, and knockdown of FMNL1 could inhibit ccRCC cell proliferation, migration and invasion, which might be used as a new effective therapeutic strategy to inhibit the progression of ccRCC.

show abstract

Formin-like 1 (FMNL1) Is Associated with Glioblastoma Multiforme Mesenchymal Subtype and Independently Predicts Poor Prognosis

Cited by 14 publications

References 47 publications

FMNL1 Exhibits Pro-Metastatic Activity via CXCR2 in Clear Cell Renal Cell Carcinoma

FMNL1 Exhibits Pro-Metastatic Activity via CXCR2 in Clear Cell Renal Cell Carcinoma

FHOD1 and FMNL1 formin proteins in intestinal gastric cancer: correlation with tumor-infiltrating T lymphocytes and molecular subtypes

Quantitative proteomic analysis reveals sophisticated metabolic alteration and identifies FMNL1 as a prognostic marker in clear cell renal cell carcinoma

Contact Info

Product

Resources

About