Formin Proteins FHOD1 and INF2 in Triple-Negative Breast Cancer: Association With Basal Markers and Functional Activities

Heuser, Vanina D.; Mansuri, Naziha; Mogg, Jasper; Kurki, Samu; Repo, Heli; Kronqvist, Pauliina; Carpén, Olli; Gardberg, Maria

doi:10.1177/1178223418792247

Cited by 20 publications

(19 citation statements)

References 38 publications

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“…However the basal expression of INF2 and FHOD1 may be as important. Both INF2 and FHOD1 have earlier been found to participate in migration or invasion and to be upregulated in clinical cancer tissues in basal-like breast cancer [15], and FHOD1 has additionally been found expressed in oral squamous cell carcinoma and melanoma, also with participation in migration/invasion in vitro [13,20].…”

Section: Discussionmentioning

confidence: 99%

“…From this cohort, we analyzed the 93 samples that had an integrated diagnosis of glioblastoma, IDH-wildtype according to the WHO 2016 classification [ 14 ]. The slides were stained by the streptavidin-peroxidase method; using a Labvision staining device (Thermo Fisher Scientific, Fremont, CA) with a Bright Vision Poly-HRP-anti-mouse/rabbit kit (Immunologic, Duiven, the Netherlands) as described previously [ 15 ]. Briefly, antigen retrieval for INF2 staining was carried out by microwaving the slides in a pH 9 buffer.…”

Section: Methodsmentioning

confidence: 99%

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Multiple formin proteins participate in glioblastoma migration

et al. 2020

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Background: The prognosis of glioblastoma remains poor, related to its diffuse spread within the brain. There is an ongoing search for molecular regulators of this particularly invasive behavior. One approach is to look for actin regulating proteins that might be targeted by future anti-cancer therapy. The formin family of proteins orchestrates rearrangement of the actin cytoskeleton in multiple cellular processes. Recently, the formin proteins mDia1 and mDia2 were shown to be expressed in glioblastoma in vitro, and their function could be modified by small molecule agonists. This finding implies that the formins could be future therapeutic targets in glioblastoma. Methods: In cell studies, we investigated the changes in expression of the 15 human formins in primary glioblastoma cells and commercially available glioblastoma cell lines during differentiation from spheroids to migrating cells using transcriptomic analysis and qRT-PCR. siRNA mediated knockdown of selected formins was performed to investigate whether their expression affects glioblastoma migration. Using immunohistochemistry, we studied the expression of two formins, FHOD1 and INF2, in tissue samples from 93 IDH-wildtype glioblastomas. Associated clinicopathological parameters and follow-up data were utilized to test whether formin expression correlates with survival or has prognostic value. Results: We found that multiple formins were upregulated during migration. Knockdown of individual formins mDia1, mDia2, FHOD1 and INF2 significantly reduced migration in most studied cell lines. Among the studied formins, knockdown of INF2 generated the greatest reduction in motility in vitro. Using immunohistochemistry, we demonstrated expression of formin proteins FHOD1 and INF2 in glioblastoma tissues. Importantly, we found that moderate/high expression of INF2 was associated with significantly impaired prognosis. Conclusions: Formins FHOD1 and INF2 participate in glioblastoma cell migration. Moderate/high expression of INF2 in glioblastoma tissue is associated with worse outcome. Taken together, our in vitro and tissue studies suggest a pivotal role for INF2 in glioblastoma. When specific inhibiting compounds become available, INF2 could be a target in the search for novel glioblastoma therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Multiple formin proteins participate in glioblastoma migration

et al. 2020

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“…In a study on the MDA-MB−231 and BT−549 TNBCs (triple-negative breast cancer) cell lines, Heuser et al have found that low levels of FHOD1 inhibited cell proliferation and migration. 32 Similarly, studies conducted by Jurmeister et al on breast cancer cells with a reduced level of FHOD1 allowed to present its importance in the context of EMT. The author has shown that FHOD1 regulates MLC2, which expression stimulates SRF-dependent transcription while silencing of FHOD1 significantly affects the disturbance and reduction of intracellular accumulation of G-actin, which reduces the motor properties of cells.…”

Section: Discussionmentioning

confidence: 97%

“… 52 In the case of basal-like breast cancer tissue, the high level of FHOD1 was also presented. 32 Clinical trials show that an increase in mortality in patients with oncological diseases is often associated with the formation of metastases. 4 The actin network is involved in this process, while its dynamic is determined by the proteins accompanying microfilaments like formin.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of FHOD1 Inhibits Metastatic Potential in A549 Cells

Hałas‐Wiśniewska¹,

Izdebska²,

Zielińska³

et al. 2021

CMAR

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“…Formin homology two domain-containing protein one or FHOD1, is a crucial regulator of cellular actin dynamics [6]. Previous studies by us and others implicate FHOD1 as an essential participant in cancer cell migration, invasion, and stress fiber formation [7][8][9][10]. FHOD1 has been implicated as one of the crucial genes linked with advanced disease and metastasis in GC patients [11].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Formin Proteins FHOD1 and INF2 in Triple-Negative Breast Cancer: Association With Basal Markers and Functional Activities

Cited by 20 publications

References 38 publications

Multiple formin proteins participate in glioblastoma migration

Multiple formin proteins participate in glioblastoma migration

Downregulation of FHOD1 Inhibits Metastatic Potential in A549 Cells

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

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