Jin, Kideok Publications
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Item The role of CXCL1 in crosstalk between endocrine resistant breast cancer and fibroblast.(Molecular Biology Reports, 2024-02-23) Pandithar, Sneha*; Galke, Daniel*; Akume, Ahone*; Belyakov, Artem*; Lomonaco, Dominick*; Guerra, Amirah A*; Park, Jay*; Reff, Olivia*; Jin, KideokBackground: ER positive breast cancer is currently targeted using various endocrine therapies. Despite the proven therapeutic efficacy, resistance to the drug and reoccurrence of tumor appears to be a complication that many patients deal with. Molecular pathways underlying the development of resistance are being widely studied. Methods and results: In this study, using four established endocrine resistant breast cancer (ERBC) cell lines, we characterized CXCL1 as a secreted factor in crosstalk between ERBC cells and fibroblasts. Protein array revealed upregulation of CXCL1 and we confirmed the CXCL1 expression by real-time qRT-PCR and U-Plex assay. Co-culturing ERBC cells with fibroblasts enhanced the cell growth and migration compared to monoculture. The crosstalk of ERBC cells with fibroblasts significantly activates ERK/MAPK signaling pathway while reparixin, CXCR1/2 receptor inhibitor, attenuates the activity. Reparixin displayed the ERBC cell growth inhibition and the combination treatment with reparixin and CDK4/6 inhibitor (palbociclib and ribociclib) increased these inhibitory effect. Conclusions: Taken together, our study implicates CXCL1 as a critical role in ERBC growth and metastasis via crosstalk with fibroblast and cotargeting CXCR1/2 and CDK4/6 could potentially overcome endocrine resistant breast cancer.Item Addendum: Crosstalk between triple negative breast cancer and microenvironment.(Oncotarget, 9/15/2023) Smrekar, Karly*; Belyakov, Artem*; Jin, KideokItem Overview of the therapeutic strategies for ER positive breast cancer.(Biochemical Pharmacology, 2023-06) Blakely, Brianna*; Shin, Seobum*; Jin, KideokEstrogen Receptor is the driving transcription factor in about 75% of all breast cancers, which is the target of endocrine therapies, but drug resistance is a common clinical problem. ESR1 point mutations at the ligand binding domain are frequently identified in metastatic tumor and ctDNA (Circulating tumor DNA) derived from ER positive breast cancer patients with endocrine therapies. Although endocrine therapy and CDK4/6 inhibitor therapy have demonstrated preclinical and clinical benefits for breast cancer, the development of resistance remains a significant challenge and the detailed mechanisms, and potential therapeutic targets in advanced breast cancer yet to be revealed. Since a crosstalk between tumor and tumor microenvironment (TME) plays an important role to grow tumor and metastasis, this effect could serve as key regulators in the resistance of endocrine therapy and the transition of breast cancer cells to metastasis. In this article, we have reviewed recent progress in endocrine therapy and the contribution of TME to ER positive breast cancer.Item Crosstalk between triple negative breast cancer and microenvironment.(Oncotarget, 3/31/2023) Smrekar, Karly*; Belyakov, Artem*; Jin, KideokAlthough many advances have been made in the treatment of breast cancer, for the triple negative breast cancer (TNBC) these therapies have not significantly increased overall survival. Tumor microenvironment (TME) plays an essential role to develop and control TNBC progression. Many preclinical and clinical studies are ongoing to treat patients with TNBC disease, but the effective therapies are currently not available. Here, we have reviewed recent progress in understanding of TNBC and advance in defining mechanisms of TNBC therapies and potential therapeutic strategies to overcome TNBC.Item Cytokines secreted by stromal cells in TNBC microenvironment as potential targets for cancer therapy.(Cancer Biology & Therapy, 6/2/2020) Malone, Marie K*; Smrekar, Karly*; Park, Sunju; Blakely, Brianna*; Walter, Alec*; Nasta, Nicholas*; Park, Jay*; Considine, Michael; Danilova, Ludmila V; Pandey, Niranjan B; Fertig, Elana J; Popel, Aleksander S; Jin, KideokIn triple-negative breast cancer (TNBC), the lack of therapeutic markers and effective targeted therapies result in an incurable metastatic disease associated with a poor prognosis. Crosstalks within the tumor microenvironment (TME), including those between cancer and stromal cells, affect the tumor heterogeneity, growth, and metastasis. Previously, we have demonstrated that IL-6, IL-8, and CCL5 play a significant role in TNBC growth and metastasis. In this study, we performed a systematic analysis of cytokine factors secreted from four stromal components (fibroblasts, macrophages, lymphatic endothelial cells, and blood microvascular endothelial cells) induced by four TNBC cell types. Through bioinformatic analysis, we selected putative candidates of secreted factors from stromal cells, which are involved in EMT activity, cell proliferation, metabolism, and matrisome pathways. Among the candidates, LCN2, GM-CSF, CST3, IL-6, IL-8, and CHI3L1 are ranked highly. Significantly, Lipocalin-2 (LCN2) is upregulated in the crosstalk of stromal cells and four different TNBC cells. We validated the increase of LCN2 secreted from four stromal cells induced by TNBC cells. Using a specific LCN2 antibody, we observed the inhibition of TNBC cell growth and migration. Taken together, these results propose secreted factors as molecular targets to treat TNBC progression via crosstalk with stromal components.