Over-expression of FSIP1 promotes breast cancer progression and confers resistance to docetaxel via MRP1 stabilization

Abstract

Fibrous sheath-interacting protein 1 (FSIP1) functions centrally in breast carcinogenesis and progression, although its exact role remains to be clarified. Therefore, we sought to establish a correlation between the clinico-pathological features of breast cancer and FSIP1 expression in breast cancer tissues, as well as to validate its role in tumor progression and chemo-resistance. We analyzed FSIP1 expression in the breast cancer and para-tumor tissues by immunohistochemistry. We performed MTT, Caspase-Glo 3/7 Assay, Annexin V staining, wound healing and trans-well assays to evaluate cellular apoptosis, proliferation, migration and invasion in FSIP1 knockout and wild-type breast cancer cell lines. Additionally, we examined the effects of FSIP1 on docetaxel sensitivity in a nude mice model transplanted with control or FSIP1 knockout breast cancer cells, and also evaluate its role in tumor metastasis. FSIP1 and MRP1 interaction was determined by co-immunoprecipitation and mass spectrometry. We found that breast cancer cells and tissues consistently demonstrated elevated FSIP1 expressions, which correlated with poor overall survival. Notably, patients with high FSIP1 expression in their tumors undergoing docetaxel neoadjuvant chemotherapy had shorter disease-free survival. FSIP1 knockout in breast cancer cells significantly increased their sensitivity to docetaxel both in vitro and in vivo. Mechanistically, FSIP1 bound to the multidrug resistance protein 1 (MRP1) and stabilized it, and knocking out FSIP1 decreased MRP1 expression and increased cellular docetaxel accumulation. In sum, FSIP1 promotes breast carcinogenesis and mediates docetaxel resistance, and may serve as a novel target in the development of breast cancer therapies.

Maslinic Acid Enhances Docetaxel Response in Human Docetaxel-Resistant Triple Negative Breast Carcinoma MDA-MB-231 Cells via Regulating MELK-FoxM1-ABCB1 Signaling Cascade

“…For measurement of cellular drug accumulation, high performance liquid chromatography (HPLC) analysis was conducted according to the previous study (Yan et al, 2019). Cells were incubated with 1 mg/ml DOC at 37°C for 2 h, and sonicated in 0.2% SDS (sodium dodecyl sulfate)/PBS (phosphate buffered saline) for 15 min.…”

VWCE Functions as a Tumor Suppressor in Breast Cancer Cells

“…Use image software to quantify and analyze the width of the gap. The average wound size represents the level of relative cell migration (22).…”

Deficiency in Dipeptidyl Peptidase-4 Promotes Chemoresistance Through the CXCL12/CXCR4/mTOR/TGFβ Signaling Pathway in Breast Cancer Cells

“…Chemotherapy is widely used to treat breast cancer patients [23], and most cancer-related deaths are linked to resistance to chemotherapy. Multidrug resistance (MDR) has been considered as a major determinant in cancer chemotherapy [24][25][26]. ATP-binding cassette (ABC) transporters are the largest family of transmembrane proteins and play a vital role in the development of multidrug resistance and chemoresistance [27] by removing a wide array of commonly employed chemotherapeutic drugs from cancer cells [28].…”