Investigating the effect of a small molecule, Inhibitor of Nuclear Import (INI-43) as a pan-cancer treatment
type: CreativeWork
description: Karyopherin beta 1 (KPNβ1) is a nuclear import protein that transports cargo molecules from the cytoplasm into the nucleus and plays an important role in other cellular processes such as mitosis and mitotic spindle assembly, DNA replication and cell cycle progression. Previous studies in our laboratory have reported that KPNβ1 is overexpressed in cervical and oesophageal cancer and is important for cancer cell survival and function, suggesting that inhibiting KPNβ1 may be a potential targeted anti-cancer strategy. An in silico screen identified a small molecule inhibitor, Inhibitor of Nuclear Import (INI-43) as an inhibitor of KPNβ1-mediated nuclear import and showed anti-cancer effects against cervical and oesophageal cancer cells using both cell culture and animal models. In this study, we expanded our investigations by determining KPNβ1 expression using bioinformatic analyses and Western blotting, and by investigating the effects of INI-43 in multiple cancer types grown in cell culture to ascertain the potential of KPNβ1 as a pan-cancer therapeutic target. In addition, we determined the ability of INI-43 to interact with KPNβ1 using the biophysical assay - Cellular Thermal Shift Assay (CETSA). Bioinformatic analyses using patient data revealed that KPNβ1 mRNA was significantly overexpressed in multiple cancer tissue compared to non-cancer tissue, including breast cancer, colon cancer, lung cancers and uterine cancers. Interestingly, we also found using bioinformatic approaches, that more than 50% of the cancers, for which data was available to us, show poorer patient survival when KPNβ1 is highly expressed. In vitro analysis using Western blotting on chosen cultured cell lines of different tissue origin revealed that KPNβ1 is overexpressed in multiple cancer types at the proteomic level, including liver cancer, gastric cancer, osteosarcoma and fibrosarcoma. These results suggest that KPNβ1 is a promising diagnostic/prognostic marker for a broad range of cancer ty…
abstract: Karyopherin beta 1 (KPNβ1) is a nuclear import protein that transports cargo molecules from the cytoplasm into the nucleus and plays an important role in other cellular processes such as mitosis and mitotic spindle assembly, DNA replication and cell cycle progression. Previous studies in our laboratory have reported that KPNβ1 is overexpressed in cervical and oesophageal cancer and is important for cancer cell survival and function, suggesting that inhibiting KPNβ1 may be a potential targeted anti-cancer strategy. An in silico screen identified a small molecule inhibitor, Inhibitor of Nuclear Import (INI-43) as an inhibitor of KPNβ1-mediated nuclear import and showed anti-cancer effects against cervical and oesophageal cancer cells using both cell culture and animal models. In this study, we expanded our investigations by determining KPNβ1 expression using bioinformatic analyses and Western blotting, and by investigating the effects of INI-43 in multiple cancer types grown in cell culture to ascertain the potential of KPNβ1 as a pan-cancer therapeutic target. In addition, we determined the ability of INI-43 to interact with KPNβ1 using the biophysical assay - Cellular Thermal Shift Assay (CETSA). Bioinformatic analyses using patient data revealed that KPNβ1 mRNA was significantly overexpressed in multiple cancer tissue compared to non-cancer tissue, including breast cancer, colon cancer, lung cancers and uterine cancers. Interestingly, we also found using bioinformatic approaches, that more than 50% of the cancers, for which data was available to us, show poorer patient survival when KPNβ1 is highly expressed. In vitro analysis using Western blotting on chosen cultured cell lines of different tissue origin revealed that KPNβ1 is overexpressed in multiple cancer types at the proteomic level, including liver cancer, gastric cancer, osteosarcoma and fibrosarcoma. These results suggest that KPNβ1 is a promising diagnostic/prognostic marker for a broad range of cancer ty…
author: Rahman, Shabita
keywords: Medicine
date published: 2024
date modified: 2026-07-22T22:23:22Z
provider: University of Cape Town
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Department of Integrative Biomedical Sciences (IBMS)

PropertyValue
property ID: Handle
value: http://hdl.handle.net/11427/40367