Year: 2020
Type: article
Abstract: IQGAP1 is a scaffold protein involved in a range of cellular activities, including migration, invasion, adhesion and proliferation. It is also oncogenic in a variety of cancers, promoting primary tumor growth and invasiveness. However, the role of IQGAP1 in tumor progression and metastasis remains unclear. In this study, we use both knockdown and knockout of IQGAP1 to investigate its role in the metastatic cascade of both melanoma and breast cancer cells in vivo. We find that reduction of IQGAP1 expression decreases the formation of both spontaneous and experimental metastases, without limiting primary or metastatic tumor growth. Furthermore, IQGAP1 knockout significantly inhibits extravasation of tumor cells from circulation, possibly involving invadopodial function. By expressing mutant forms of IQGAP1 in a knockout context, we also determine that IQGAP1's pro-metastatic functions are dependent on multiple domains and functions. These data demonstrate that IQGAP1 is crucial for metastasis in vivo through regulation of extravasation and suggest that it may represent a valid therapeutic target for inhibiting metastasis.
Source: Scientific Reports
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,870
Funders: U.S. Department of Defense, Howard Hughes Medical Institute, U.S. Department of Health and Human Services, Damon Runyon Cancer Research Foundation, Massachusetts Institute of Technology, Ludwig Institute for Cancer Research, National Institutes of Health, Ludwig Center for Molecular Oncology, Ludwig Center at Harvard, National Institute of General Medical Sciences, Congressionally Directed Medical Research Programs
OpenAlex ID: W3006299474