BACH1 (BTB Domain And CNC Homolog 1)

Additional investigations confirm that BACH1 specifically mitigates cisplatin-triggered tumor cell death by regulating the "BACH1-LDHA/McT4-lactate metabolism-ferroptosis inhibition" axis, leading to cisplatin resistance in ICC cells. Our findings revealed that through this regulatory axis, BACH1 induces cisplatin resistance and may serve as a therapeutic target in ICC.

BACH1-driven CM-TAMs activate TBLCs via the ANGPTL4-SDC4 signaling axis, promoting stemness and cholesterol accumulation, ultimately driving malignant progression in chordoma. These findings uncover a previously unrecognized tumor-immune-metabolic interaction and suggest potential therapeutic targets for this disease.

Furthermore, in vivo mouse allograft experiments showed that Bach1 knockout cells exhibited reduced tumor growth and fewer lung metastases, accompanied by altered expression of EMT markers and modulation of cytokine-driven immune signaling. Collectively, these findings suggest that BACH1 plays a crucial role in BC progression and metastasis, at least in part, through two complementary mechanisms, EMT activation and immune microenvironment modulation via cytokine signaling.

Moreover, the PLK1/BACH1 axis confers resistance to Vemurafenib, a BRAFV600E inhibitor, in melanoma. In light of this finding, we attempted an innovative pharmacological combination targeting both BRAFV600E and PLK1, identifying a synergistic efficiency to this approach to suppress tumor growth. Overall, we have discovered a novel function of PLK1 that is independent of the cell cycle, which could pave new ways for melanoma therapies.

Downregulation of either BACH1 or PDP1 suppressed the PI3K-AKT-mTOR signaling pathway, and a PI3K activator effectively reversed the inhibition of HCC cell proliferation induced by BACH1 or PDP1 downregulation. Collectively, our present study reveals a novel regulatory axis of BACH1-PDP1-PI3K-AKT-mTOR, thereby providing potential intervention targets and a theoretical basis for the molecular precision therapy of HCC.

Analysis of pan-cancer immunotherapy cohorts revealed a significant correlation between CXCR2 + VNN2 + Neu phenotypic transition and immunotherapy resistance in patients. We finally constructed a deep learning model named Deepsurv to accurately stratify pan-cancer patients based on the CXCR2 + VNN2 + Neu Phenotypic Transition Gene Regulatory Network (CVN-GRN) and predict the prognosis of the patients, which achieved the desired results.

The BAF53A-BACH1-GCLM axis constitutes a novel egulatory pathway that integrates chromatin remodeling, transcriptional regulatione, and ferroptosis resistance in ESCC. Targeting this axis may offer a promising approach to exploit metabolic vulnerabilities and enhance ferroptosis sensitivity in ESCC treatment.

It also demonstrated ERBB2 amplification, as well as mutations in ATRX and BACH1. Accurate recognition of such tumors is crucial due to their propensity for aggressive behavior and the availability of potential targeted therapeutic options.

The MBFCGs risk model is a promising prognostic tool for LGG, offering insights into underlying mechanisms and new directions for immunotherapy strategies. Assessment of MBFCGs for individual LGG patients may provide clues for developing new immunotherapy strategies.

Multivariable Cox regression analyses, adjusting for potential prognostic factors such as sex, Eastern Cooperative Oncology Group performance status, and tumor size and stage, revealed that CARS1-AS1 (adjusted hazard ratio [HR] 0.33; 95% confidence interval [CI], 0.15-0.73; P =0.0061) and miR-142-5p (adjusted HR 0.79; 95% CI, 0.61-1.01; P = 0.0581) were associated with improved overall survival. We identified potential Ex-smRNA biomarkers involved in PDAC progression and prognosis that reflect key molecular alterations in PDAC and may serve as clinically relevant biomarkers for disease monitoring.

HPPE incubation inhibited proliferation, promoted apoptosis, and induced G2/M arrest, indicating a potential synergistic effect with temozolomide in GBM cells...In vivo experiments revealed that HPPE prolonged the survival time of mice, inhibited Wnt/β-catenin pathway activity and had a synergistic effect with TMZ in a xenograft model. In summary, these findings provide potential combined therapeutic strategies for glioma by targeting the C-terminus of BACH1 and inhibiting the activation of WNT signaling.

Furthermore, unlike many degraders, our molecules recruit NSD2 to a different surface of FBXO22 than the known FBXO22 substrate BACH1, allowing for concurrent complex formation and degradation of both the neosubstrate and endogenous substrates. Overall, we demonstrate the biochemical and structural basis for NSD2 degradation, revealing key principles for efficient and selective TPD by SCF-FBXO22.