Purpose: Triple-negative breast cancer (TNBC) is one of the most aggressive breast cancer subtypes, and treatment options are limited because of the lack of signature molecules and heterogeneous properties of cancer. COL8A1 expression is higher in breast cancer than in normal tissues and is strongly correlated with worse overall survival in patients with breast cancer. However, the biological function of COL8A1 on cancer progression is not fully understood. In this study, we investigated the biological function of COL8A1 on TNBC progression.
Methods: COL8A1-deficient cells were generated using the CRISPR-Cas9 system. The tumor growth and metastasis of TNBC cells were evaluated using three-dimensional culture (3D) methods and xenograft mouse models. The activation of focal adhesion kinase (FAK)/Src by COL8A1 in TNBC cells was evaluated by immunoblotting.
Results: COL8A1 expression was primarily distributed into TNBC cell lines. Further, relapse-free survival in TNBC patients with the MSL subtype was strongly associated with the COL8A1 expression. MDA-MB-231 and Hs578T cells, classified as the MSL subtype, strongly express COL8A1, and COL8A1 protein expression was induced by hypoxia in both cell lines. Loss of COL8A1 expression inhibited spheroid /tumor growth and metastasis in vitro and in vivo. Further, exogenous COL8A1 promoted TNBC growth via the FAK/Src activation. Finally, the spheroid growth of MDA-MB-231 and Hs578T cells was inhibited by defactinib, a FAK inhibitor, without cytotoxicity.
Conclusion: These results indicate that COL8A1-mediated FAK/Src activation produces a more aggressive phenotype in TNBC, and its target inhibition may be an efficacious treatment for TNBC.
Department of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, United States.
DNA interstrand cross-links (ICLs) are the sources of the cytotoxicity of many anticancer agents. Selenium compounds showed great potential as anticancer drugs. In this work, we synthesized a binaphthalene analog containing phenyl selenide (-SePh) as the leaving group and investigated its photochemical reactivity toward DNA as well as its cytotoxicity and selectivity.
Radiation therapy (RT) is one of the core therapies for current cancer management. However, the emergence of radioresistance has become a major cause of radiotherapy failure and disease progression. Therefore, overcoming radioresistance to achieve highly effective treatment for refractory tumors is significant yet challenging.
Exosome-based drug delivery holds significant promise for cancer chemotherapy. However, current methods for loading drugs into exosomes are inefficient and cost-prohibitive for practical application. In this study, boron clusters are mixed with doxorubicin (DOX) and exosomes, enabling the efficient encapsulation of DOX into exosomes through a superchaotropic effect.
Adipocytes represent a significant proportion of breast tissue, comprising between 3.7 and 37% of stromal tissue. They play a pivotal role in metabolic regulation, energy supply, metabolic regulation, support effects, and cytokine release within the breast.
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre University Health Network, 700 University Ave, Toronto, ON, M5G 1Z5, Canada.
Purpose: In early-stage breast cancer, steatotic liver disease (SLD) is associated with increased recurrence, cardiovascular events, and non-cancer death. Endocrine therapy (ET) increases the risk of SLD. The impact of cyclin-dependent kinases 4/6 inhibitors (CDK4/6i) on SLD and prognostic association in metastatic breast cancer is unknown.
