KPNB1 (Karyopherin subunit beta-1)

Thus, our work identifies a central regulatory layer of NE repair centered on LRRC59 and KPNB1. We propose that altered LRRC59 levels and deregulated nuclear transport coordinately compromise NE repair, driving genome instability and cancer development.

Besides, AQP5+ tumor cells also redirect the UC to the TCA cycle, which stores the saved nitrogen in glutamine by promoting glutamate-ammonia ligase (GLUL) stability. This study uncovers the evidence of AQP5+ cancer stem cells impairing NK cell cytotoxicity by changing self-metabolism patterns.

A logistic regression model combining the five available sEV proteins and two conventional markers demonstrated 78.26% sensitivity and 96.67% specificity for early detection (AUC = 0.961). Our findings nominate these sEV protein signatures as promising noninvasive biomarkers for CRC diagnosis.

In TNBC mouse models, ARID1B knockout (KO) significantly reduces tumor growth and enhances PARP inhibitor efficacy. Collectively, these findings uncover an undocumented mechanism for ARID1B nuclear translocation and reveal that blockade of ARID1B nuclear translocation can be a new therapeutic strategy for TNBC.

Sphingosine and constrained analogs like FTY720 and SH-BC-893 restrain tumor growth through incompletely defined mechanisms that include protein phosphatase 2A (PP2A) activation...Simultaneous PP2A activation and importin inhibition reduces nuclear levels of proteins that drive cancer progression and therapeutic resistance such as JUN, YAP, MYC, androgen receptor, hnRNPA1, and NF-κB under conditions where compounds that target PP2A or KPNB1 individually are inactive. These findings provide new insights into sphingolipid biology and highlight a possible path toward cancer therapeutics that could overcome drug resistance.

Further studies verify WA as an effective antitumor drug candidate via blocking VCP nuclear localization to impact on the DDR pathway in vivo. Our findings underly the unclear VCP's role in DDR in a KPNB1-dependent manner and provide an important theoretical basis for developing small-molecule inhibitors targeting this process.

In conclusion, this study demonstrates that NAT10 upregulates KPNB1 expression through ac4C modification, thereby promoting RT resistance in NSCLC via PD-L1 nuclear translocation. These findings reveal a novel mechanism underlying RT resistance in NSCLC.

Notably, the inhibition of KPNB1 by IPZ significantly enhanced the sensitivity of both AML cell lines and patient-derived cells to venetoclax in vitro and in xenograft mice models...Inhibition of KPNB1 resulted in impaired nuclear import of HMGB2, eventually leading to compromised DNA damage repair in AML cells. Overall, our findings elucidate the essential roles of KPNB1 in AML cells through the HMGB2-DNA damage repair axis and highlight a promising therapeutic target for AML intervention.

Si-KPNB1 reversed the effects of KPNA2 overexpression on macrophages and gastric cancer cells. KPNA2 promoted the M2 polarization of macrophages by upregulating KPNB1, thereby inducing the proliferation and metastasis of gastric cancer.

In our efforts to enhance sensitivity to PARP inhibitors, we identified clofarabine (CLF) as a potential therapy for drug-resistant ovarian cancer and nuclear trafficking of Cathepsin L (CTSL) as a treatment- responsive biomarker. Using PARP inhibitor-sensitive and -resistant OC cell lines, ex vivo cultures of patient-derived ovarian ascites (OVA), primary ovarian tumors, and xenografts (PDX), we found that CLF monotherapy induces nuclear CTSL (nCTSL) in CLF-responsive cells (CLF-r) and sensitizes them to PARP inhibitors olaparib and rucaparib...In these samples, inhibiting CRM1 with KPT8602 restored synergy between CLF and PARP inhibitors. In vivo, CLF-r and CLF-nr PDX models exhibited enhanced DDR, reduced tumor burden, and prolonged survival with the CLF+olaparib combination. These findings suggest the CLF+olaparib combination is a promising therapeutic strategy for drug-resistant OC by inducing DDR through CTSL nuclear localization.

In conclusion, the molecular mechanism underlying the TMEM209/KPNB1/Wnt/β-catenin axis in HCC progression was elucidated. TMEM209 is a potential biomarker and therapeutic target for HCC.

We delineate the unconventional function and subcellular location of ADCY7, highlighting its pivotal role in T cell-mediated immunity in HCC and its potential as a promising treatment target.