ArticleCancer research and treatment2019
Upregulation of PITX2 Promotes Letrozole Resistance Via Transcriptional Activation of IFITM1 Signaling in Breast Cancer Cells.
Article in Cancer research and treatment, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Interferon-induced transmembrane (IFITM) proteins at the tumour-immune interface: A four-axis framework for their context-dependent roles.Clinical and translational medicine · 2026Review
- Chronic prostatitis/chronic pelvic pain syndrome impairs erectile function by inducing apoptosis in a rat model of experimental autoimmune prostatitis.International journal of impotence research · 2025Article
- The role and mechanism of IFITM1 in developing acquired cisplatin resistance in small cell lung cancer.Heliyon · 2024Article
- Identification of a CircRNA-miRNA-mRNA Network and Integrated Analysis of Immune Infiltration in Oral Squamous Cell Carcinoma.Journal of Cancer · 2023Article
- Co-expression of DDR2 and IFITM1 promotes breast cancer cell proliferation, migration and invasion and inhibits apoptosis.Journal of cancer research and clinical oncology · 2022Article
- Mammography radiomics features at diagnosis and progression-free survival among patients with breast cancer.British journal of cancer · 2022Article
- PITX2 DNA-Methylation: Predictive versus Prognostic Value for Anthracycline-Based Chemotherapy in Triple-Negative Breast Cancer Patients.Breast care (Basel, Switzerland) · 2021Article
- Disrupting interferon-alpha and NF-kappaB crosstalk suppresses IFITM1 expression attenuating triple-negative breast cancer progression.Cancer letters · 2021Article
- The significance of homeodomain transcription factor 2 in colon cancer cells.Biomedical engineering online · 2021Article
- Chemoresistance in breast cancer: PI3K/Akt pathway inhibitors vs the current chemotherapy.American journal of cancer research · 2021Review
- Downregulation of PITX2 inhibits the proliferation and migration of liver cancer cells and induces cell apoptosis.Open life sciences · 2021Article
- Deciphering the Roles of IFITM1 in Tumors.Molecular diagnosis & therapy · 2020Review
- Interferon-induced transmembrane protein 1 (IFITM1) is essential for progression of laryngeal squamous cell carcinoma in an Osteopontin/NF-κB-dependent manner.Cancer biomarkers : section A of Disease markers · 2020Article
- PITX2 enhances progression of lung adenocarcinoma by transcriptionally regulating WNT3A and activating Wnt/β-catenin signaling pathway.Cancer cell international · 2019Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
purposeAlthough the interferon α (IFNα) signaling and the paired-like homeodomain transcription factor 2 (PITX2) have both been implicated in the progression of breast cancer (BCa), it remains obscure whether these two pathways act in a coordinated manner. We therefore aimed to elucidate the expression and function of PITX2 during the pathogenesis of endocrine resistance in BCa. MATERIALS AND
methodsPITX2 expression was assessed in BCa tissues using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunohistochemistry and in experimentally induced letrozole-resistant BCa cells using RT-qPCR and immunoblotting. Effects of PITX2 deregulation on BCa progression was determined by assessing MTT, apoptosis and xenograft model. Finally, using multiple assays, the transcriptional regulation of interferon-inducible transmembrane protein 1 (IFITM1) by PITX2 was studied at both molecular and functional levels.
resultsPITX2 expression was induced in letrozole-resistant BCa tissues and cells, and PITX2 induction by IFNα signaling powerfully protected BCa cells against letrozole insult and potentiated letrozole-resistance. Mechanistically, PITX2 enhanced IFNα-induced AKT activation by transactivating the transcription of IFITM1, thus rendering BCa cells unresponsive to letrozoleelicited cell death. Additionally, ablation of IFITM1 expression using siRNA substantially abolished IFNα-elicited AKT phosphorylation, even in the presence of PITX2 overexpression, thus sensitizing BCa cells to letrozole treatment.
conclusionThese results demonstrate that constitutive upregulation of PITX2/IFITM1 cascade is an intrinsic adaptive mechanism during the pathogenesis of letrozole-resistance, and modulation of PITX2/IFITM1 level using different genetic and pharmacological means would thus have a novel therapeutic potential against letrozole resistance in BCa.
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