MAP4 (Microtubule Associated Protein 4)

Here, we performed a synthetic lethal drug screening in an approved drug library with ARID1A isogenic CRC cell lines and identified estramustine phosphate sodium (EMP), an FDA approved antimicrotubule chemotherapy drug, as a synthetic lethal partner of ARID1A...Furthermore, we identified that MAP4 is phosphorylated by PI3K, which is activated by ARID1A loss. These findings highlight MAP4 as a key regulator of microtubule dynamics in ARID1A-deficient cells and unveil a novel synthetic lethality relationship between ARID1A and EMP.

Our findings identify ARIH1 as a novel regulator of microtubule dynamics in breast cancer. ARIH1 suppression enhances paclitaxel sensitivity, highlighting its potential as both a therapeutic target and a biomarker for predicting treatment response and patient outcomes in breast cancer.

MAP4 is highly expressed in lung adenocarcinoma; it may affect prognosis by promoting the migration and invasion of cancer cells. We developed a nomogram including clinical factors and MAP4 expression that can be used for prognosis prediction in patients with lung adenocarcinoma. MAP4 participates in radiation resistance in lung adenocarcinoma by regulating the radiation-induced EMT process. MAP4 may serve as a biomarker for lung adenocarcinoma prognosis evaluation and as a new target for improving radiosensitivity.

On the other hand, the protrusions of tau-expressing cells had the fewest branches. These results suggest that the properties of microtubules, which are regulated by MAPs, contribute to the morphogenesis of neurites.

This study provided evidence that FBXW7 loss of function promoted ESCC via MAP4 overexpression and ERK phosphorylation, and this novel FBXW7/MAP4/ERK axis may be an efficient target for ESCC treatment.

Further evidence demonstrated that the up-regulation of β-catenin activity induced by the interaction between MAP4 and GSK3β possibly accounted for the pro-migration and pro-EMT effects of MAP4 on HCC cells. Taken together, these results suggest that MAP4 promotes migration, invasion, and EMT in HCC cells by regulating the GSK3β/β-catenin pathway.

Then, the control group and the knockdown group both received the combined treatment of cisplatin at a final concentration of 5 μmol/L and paclitaxel at a final concentration of 20 nmol/L. The stably knocked down MAP4 K4 expressing cells showed significantly enhanced toxicity of chemotherapeutic drugs to cancer cells. The study shows that MAP4 K4 regulates the malignant phenotypes of cancer cells and chemoresistance by regulating "cadherin switch" to promote epithelial-mesenchymal transition in A549 cells.

Additionally, troxerutin significantly decreased malondialdehyde (MDA), hydrogen peroxide (HO), NO, inducible nitric oxide synthase (iNOS) levels (P < 0.01), p-NF-κB p65/NF-κB p65, TNF-α, Pro-IL-1β, IL-6, B cell lymphoma-2 (Bcl-2)/Bcl-xl associated death promoter (Bad), Cytochrome C (Cyt C), Cleaved-caspase 9, Cleaved-caspase 3, and Cleaved-caspase 8 protein levels (P < 0.01) in the kidney tissues of cisplatin-treated rats; and increased superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), total antioxidant capacity (T-AOC) activities (P < 0.01), IL-10, Bcl-2 protein levels (P < 0.01). These results suggested that the underlying mechanism might be attributed to the regulation of Phosphoinositide 3 kinase/Protein kinase B (PI3K/AKT) pathway via enhancing MAP4 expression to attenuate cellular apoptosis, alleviating oxidative stress and inflammatory response.

Furthermore, BRINP3 interacted with microtubule-associated protein 4 (MAP4) at the protein level, and overexpression of MAP4 could partially reverse the inhibitory effect of downregulated BRINP3 on the proliferation and invasion of osteosarcoma cells, which indicates that downregulation of BRINP3 might suppress the proliferation and invasion of osteosarcoma cells by inhibiting MAP4 expression. Overall, our results demonstrate that BRINP3 functions as an oncogene within osteosarcoma through MAP4 and could therefore be used as a potential biomarker for osteosarcoma diagnostics and therapeutics.