Limiting cellular plasticity is of key importance for the therapeutic targeting metastatic breast cancer (MBC). Fibroblast growth receptor (FGFR) a critical molecule in and potent inhibitors FGFR enzymatic activity have been developed, but kinase independent functions this also contribute to MBC progression. Herein, we evaluated several find that while FGFR-targeted are effective at blocking ligand-induced cell growth, dormant cells persist eventually giving rise To more broadly target...

Abstract Metastatic breast cancer (MBC) remains a therapeutic challenge due to the persistence of minimal residual disease (MRD) and tumor recurrence. Herein we utilize model MBC that is sensitive inhibition fibroblast growth factor receptor (FGFR), resulting in robust regression pulmonary lesions upon treatment with FGFR inhibitor pemigatinib. Assessment remaining MRD revealed upregulation platelet-derived (PDGFR). Functionally, demonstrate increased response PDGF ligand stimulation...

Abstract FGFR is amplified in 20% of metastatic breast cancer cells (MBCs) where it promotes growth, sustains mesenchymal plasticity, and mediates drug resistance. Systemic inhibition kinase activity increases the numbers CD4+ CD8+ T-cells decreases abundance myeloid-derived suppressor (MDSCs) tumor microenvironment. These data indicate an immunosuppressive role signaling pathway MBCs. However, a mechanism by which blockade affects T-cell presence not well understood. decrease progression...

ABSTRACT Epithelial-mesenchymal transitions (EMTs) are thought to promote metastasis via downregulation of E-cadherin (also known as Cdh1) and upregulation mesenchymal markers such N-cadherin (Cdh2) vimentin (Vim). Contrary this, is retained in many invasive carcinomas promotes collective cell invasion. To investigate how regulates metastasis, we examined the highly metastatic, E-cadherin-positive murine 4T1 breast cancer model, together with less 4T1-related lines 4T07, 168FARN 67NR. We...

Abstract Survival of dormant, disseminated breast cancer cells contributes to tumor relapse and metastasis. Women with a body mass index greater than 35 have an increased risk developing metastatic recurrence. Herein, we investigated the effect diet-induced obesity (DIO) on primary growth progression using both systemically dormant mouse models cancer. This approach led PT pulmonary We developed novel protocol induce in Balb/c mice by combining dietary hormonal interventions thermoneutral...

SH2 containing protein tyrosine phosphatase-2 (SHP2) is recognized as a druggable oncogenic phosphatase that expressed in both tumor cells and immune cells. How cell-autonomous SHP2 contributes to an immunosuppressive microenvironment (TME) therapeutic failure of checkpoint blockades metastatic breast cancer (MBC) not fully understood. Herein, we utilized systemic inhibition inducible genetic depletion investigate reprogramming during targeting. Pharmacologic sensitized MBC growing the lung...

Abstract Breast cancer (BC) is the most diagnosed in females United States and second leading cause of related deaths among women. The fibroblast growth factor receptor (FGFR) signaling pathway frequently activated BC, making it an attractive therapeutic target, especially metastatic disease. However, clinical trials using FGFR inhibitors BC have been disappointing comparison to other types treated with these therapies. As a result, patients do not targeted option. Failure indicative...

<p>These are the figure legends for Supplementary figures 1 and 2.</p>

<p>Pemigatinib blocks FGF2-induced signaling and 3D outgrowth of D2.OR cells via inhibition FGFR1.</p>

<p>These are the figure legends for Supplementary figures 1 and 2.</p>

<div>Abstract<p>Survival of dormant, disseminated breast cancer cells contributes to tumor relapse and metastasis. Women with a body mass index greater than 35 have an increased risk developing metastatic recurrence. Herein, we investigated the effect diet-induced obesity (DIO) on primary growth progression using both systemically dormant mouse models cancer. This approach led PT pulmonary We developed novel protocol induce in Balb/c mice by combining dietary hormonal...

<p>Paracrine FGF2 can induce the outgrowth of D2.OR cells in 3D culture.</p>

<p>Pemigatinib blocks FGF2-induced signaling and 3D outgrowth of D2.OR cells via inhibition FGFR1.</p>

<div>Abstract<p>Survival of dormant, disseminated breast cancer cells contributes to tumor relapse and metastasis. Women with a body mass index greater than 35 have an increased risk developing metastatic recurrence. Herein, we investigated the effect diet-induced obesity (DIO) on primary growth progression using both systemically dormant mouse models cancer. This approach led PT pulmonary We developed novel protocol induce in Balb/c mice by combining dietary hormonal...

<p>Paracrine FGF2 can induce the outgrowth of D2.OR cells in 3D culture.</p>

Abstract Metastatic breast cancer (MBC) is the most advanced stage of cancer. Our understanding molecular mechanisms which drive MBC remain incomplete. Epithelial to mesenchymal transition (EMT) and epithelial (MET) promote drug resistance metastasis. It has been reported that fibroblast growth factor receptor 1 (FGFR1) plays a key role during EMT:MET cycle. Furthermore, FGFR1 amplified in 13% primary 20% metastatic patients. Therefore, optimizing inhibition crucial for therapeutic targeting...

Lipid accumulation is associated with breast cancer metastasis. However, the mechanisms underlying how cells increase lipid stores and their functional role in disease progression remain incompletely understood. Herein we quantified changes metabolism characterized cytoplasmic droplets metastatic versus non-metastatic cells.

<div><p>SH2 containing protein tyrosine phosphatase-2 (SHP2) is recognized as a druggable oncogenic phosphatase that expressed in both tumor cells and immune cells. How cell–autonomous SHP2 contributes to an immunosuppressive microenvironment (TME) therapeutic failure of checkpoint blockades metastatic breast cancer (MBC) not fully understood. Herein, we utilized systemic inhibition inducible genetic depletion investigate reprogramming during targeting. Pharmacologic sensitized...

<div><p>SH2 containing protein tyrosine phosphatase-2 (SHP2) is recognized as a druggable oncogenic phosphatase that expressed in both tumor cells and immune cells. How cell–autonomous SHP2 contributes to an immunosuppressive microenvironment (TME) therapeutic failure of checkpoint blockades metastatic breast cancer (MBC) not fully understood. Herein, we utilized systemic inhibition inducible genetic depletion investigate reprogramming during targeting. Pharmacologic sensitized...

<p>This is the code information for publicly available data analysis.</p>

<p>Representative dot plots for data shown in figure 4B-C and additional exhaustion marker analysis of CD4+ T cells mice bearing SHP2 manipulated 4T1 metastases.</p>

<p>Corresponding representative dot plots for the quantification in figure 2D-F and additional myeloid composition analysis study of D2.A1 model.</p>