Since the expression of LIMK2 is dysregulated in several human cancers, measuring the tissue expression of LIMK2 could potentially help diagnose cancer and predict patient prognosis. As LIMK2 could play tumour-promoting and tumour-inhibiting roles in cancer development, more investigation should be conducted to carefully evaluate whether introducing a LIMK2 inhibitor in cancer patients could slow cancer progression without posing clinical harms.

SFN plays an important role in the diagnosis of cervical cancer. SFN can regulate cervical cancer cell proliferation, apoptosis, cytoskeletal remodeling and metastasis through LIMK2/Cofilin signaling.

This review focuses on LIMK2's unique catalytic mechanism, substrate specificity and its upstream regulators at transcriptional, post-transcriptional and post-translational stages. Moreover, emerging studies have unveiled a few tumor suppressors and oncogenes as LIMK2's direct substrates, which in turn have uncovered novel molecular mechanisms by which it plays pleiotropic roles in human physiology and pathologies independent of actin dynamics.

G3BP1 was required for ESM1 mRNA stability, and ESM1 ectopic expression rescued LIMK2 or G3BP1 inhibition-induced suppression of melanoma growth and metastatic attributes. These results collectively identify the LIMK2→G3BP1→ESM1 pathway as a facilitator of melanoma tumor growth and metastasis and document that LIMK2 is a therapeutically tractable target for melanoma therapy.

There was no significant correlation of CIPN with any other SNP. A multivariate analysis showed that the cumulative dose of nab-PTX was most strongly correlated with CIPN (p<0.01).

Combination experiments with CEL_Amide and BCR::ABL TKIs imatinib, dasatinib, nilotinib, and ponatinib were synergistic for the treatment of both TOM-1 and BV-173 cells. CDKN2A/BCR::ABL1+ B-ALL cells were transplanted in mice, which were treated with combinations of CEL_Amide and nilotinib or ponatinib, which significantly prolonged their survival. Altogether, the LIMKi CEL_Amide yields activity in Ph+ ALL models when combined with BCR::ABL-targeting TKIs, showing promising synergy that warrants further investigation.

This study developed and optimised an innovative discovery approach which could be adapted for the discovery of biomarkers and molecular interactions in a range of biological and clinical studies. Furthermore, this study identified a protein signature that can be utilised as an independent prognostic method and for potential therapeutic interventions.

Finally, we confirmed upstream regulatory noncoding RNAs (ncRNAs) of LIMK2, and the PVT1 and DHRS4-AS1/miR-423-5p/LIMK2 regulatory axes were successfully constructed in LUSC. Put together, LIMK2 is a novel prognostic biomarker and correlates with tumor immune cell infiltration in LUSC, and the expression of LIMK2 is regulated by the PVT1 and DHRS4-AS1/miR-423-5p axes.

These results suggest that the mevalonate pathway activates RhoA, which in turn activates YAP and promotes OS cell resistance to MPPa-PDT therapy. Targeting the RhoA/ROCK2/LIMK2/YAP pathway can significantly improve the efficacy of MPPa-PDT treatment for OS.

As NKX3.1 is a prostate-specific tumor suppressor, preserving its levels by LIMK2 inhibition provides a tremendous opportunity for developing targeted therapy in CRPC. Further, as NKX3.1 downregulates AR transcription and inhibits AKT signaling, restoring its levels by inhibiting LIMK2 is expected to be especially beneficial by co-targeting two driver pathways in tandem, a highly desirable requisite for developing effective PCa therapeutics.

Finally, we observed a reciprocal regulation between LIM kinases (LIMK) and CDK6, a kinase known to be involved in the differentiation block of KMT2A-rearranged AML, and addition of the CDK6 inhibitor palbociclib further enhanced the anti-proliferative effect of LIMK inhibition. Together, these data suggest that LIMK are promising targets for AML therapy.

While genomically altered SPOP-bearing tumours require gene therapy, uncovering LIMK2-SPOP relationship provides a powerful opportunity to retain WT-SPOP by inhibiting LIMK2, thereby halting disease progression.

LIM kinase 2 (LIMK2), an essential molecule in p21 signal transduction, was significantly upregulated and represents a novel mechanism for hormone-independent pathogenesis of endometrial adenocarcinoma. This preclinical mouse model represents the first genetically engineered mouse model of poorly differentiated endometrial adenocarcinoma.

Moreover, we investigated the effects of apatinib treatment and VEGFR2 knockdown on osteosarcoma as well as the relevant underlying mechanism...In this study, we presented the pro-metastatic functional mechanism of VEGFR2 in osteosarcoma. VEGFR2 inhibition exhibits antitumor effects through antiangiogenic effects and inhibition of immune escape, which possibly provides potential clinical treatment for metastatic osteosarcoma.

This is the first study to show a feedback loop between PTEN and its regulator. Uncovering the LIMK2-PTEN loop provides a powerful therapeutic opportunity to retain the activity and stability of PTEN protein by inhibiting LIMK2, thereby halting the progression to CRPC, ADT-resistance and drug-resistance.

Moreover, the pharmacological inhibition of LIMK2 blocked metastatic progression in mice without affecting primary tumor growth. In sum, these results identified LIMK2 as a facilitator of distal TNBC metastasis and a potential target for preventing TNBC metastatic progression.

Lack of association was demonstrated for LIMK2, PTPN12, LRP6, PTPRJ, POLQ, BLM, MCM9 and FOCAD variants. Additional studies are required to provide conclusive evidence for SEMA4A, WIF1, HNRNPA0 c.-110G>C, and FOCAD large deletions.