The Yes-associated protein (YAP) is a major oncoprotein responsible for cell proliferation control. YAP's oncogenic activity is regulated by both the Hippo kinase cascade and uniquely by a mechanical-force-induced actin remodeling process. Inspired by reports that ovarian cancer cells specifically accumulate the phosphatase protein ALPP on lipid rafts that physically link to actin cytoskeleton, we developed a molecular self-assembly (MSA) technology that selectively halts cancer cell proliferation by inactivating YAP. We designed a ruthenium-complex-peptide precursor molecule that, upon cleavage of phosphate groups, undergoes self-assembly to form nanostructures specifically on lipid rafts of ovarian cancer cells. The MSAs exert potent, cancer-cell-specific antiproliferative effects in multiple cancer cell lines and in mouse xenograft tumor models. Our work illustrates how basic biochemical insights can be exploited as the basis for a nanobiointerface fabrication technology which links nanoscale protein activities at specific subcellular locations to molecular biological activities to suppress cancer cell proliferation.
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http://dx.doi.org/10.1021/acs.nanolett.0c04435 | DOI Listing |
Front Glob Womens Health
December 2024
WHO Department of Sexual and Reproductive Health and Research, World Health Organization, Geneva, Switzerland.
[This corrects the article DOI: 10.3389/fgwh.2024.
View Article and Find Full Text PDFFront Oncol
December 2024
Department of Gynaecologic Oncology, Center for Gynaecologic Oncology Amsterdam, Cancer Center Amsterdam, Amsterdam University Medical Centres, Amsterdam, Netherlands.
Photoacoustics
February 2025
Biomedical Engineering Department, Washington University in St Louis, United States.
Ovarian-adnexal lesions are conventionally assessed with ultrasound (US) under the guidance of the Ovarian-Adnexal Reporting and Data System (O-RADS). However, the low specificity of O-RADS results in many unnecessary surgeries. Here, we use co-registered US and photoacoustic tomography (PAT) to improve the diagnostic accuracy of O-RADS.
View Article and Find Full Text PDFGynecol Oncol Rep
December 2024
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Long Island Jewish Medical Center, Zucker School of Medicine at Hofstra/Northwell, Northwell Health, New Hyde Park, NY, United States.
The use of immunohistochemistry (IHC) and molecular pathology has been widely adopted over the past 3 decades and has aided in the precision of diagnosing gynecologic tumors. While many tumors can be diagnosed by histologic appearance on routine hematoxylin and eosin stained slides, the use of IHC has dramatically changed practice, leading to a better understanding and subtyping of gynecologic tumors. This detailed classification of tumors has aided in the implementation and development of targeted therapies.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
December 2024
Department of Urology, Kunming Children's Hospital, Kunming, Yunnan, China.
Zinc is an essential trace element in the human body, playing a crucial role in cellular metabolism.Dysregulation of zinc homeostasis can lead to abnormal cellular metabolism, contributing to diseases and closely related to tumor development. Adequate zinc intake can maintain zinc homeostasis in the body and support normal cellular metabolism.
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