Search

Your search keyword '"Kinase activity"' showing total 2 results
2 results on '"Kinase activity"'

1. HULC targets the IGF1R-PI3K-AKT axis in trans to promote breast cancer metastasis and cisplatin resistance.

Author

Zhou, Lei, Li, Hui, Sun, Tingge, Wen, Xue, Niu, Chao, Li, Min, Li, Wei, Hoffman, Andrew R., Hu, Ji-Fan, and Cui, Jiuwei

Subjects
*RNA metabolism, *PROTEIN metabolism, *SOMATOMEDIN, *CHROMOSOMES, *PHOSPHOTRANSFERASES, *RNA, *CANCER relapse, *CELL physiology, *APOPTOSIS, *TRANSFERASES, *GENES, *CISPLATIN, *CELL lines, *MICE, *ANIMALS
Abstract

Insulin-like growth factor I receptor (IGF1R) is frequently upregulated in breast cancer. Due to its intrinsic tyrosine kinase activity, aberrant activation of the IGF1R signaling axis may enhance tumor cell proliferation and cancer stemness, causing tumor relapse, metastasis and resistance to chemotherapy. We utilized a chromatin RNA in situ reverse transcription (CRIST) approach to characterize molecular factors that regulate the IGF1R network. We identified lncRNA HULC (Highly Upregulated in Liver Cancer) as a key trans-regulator of IGF1R in breast cancer cells. Loss of HULC suppressed the expression of IGF1R and the activation of its downstream PI3K/AKT pathway, while HULC overexpression activated the axis in breast cancer cells. Using a transcription-associated trap (RAT) assay, we demonstrated that HULC functioned as a nuclear lncRNA and epigenetically activated IGF1R by directly binding to the intragenic regulatory elements of the gene, orchestrating intrachromosomal interactions, and promoting histone H3K9 acetylation. The activated HULC-IGF1R/PI3K/AKT pathway mediated tumor resistance to cisplatin through the increased expression of cancer stemness markers, including NANOG, SOX2, OCT4, CD44 and ALDH1A1. In immunodeficient mice, stimulation of the HULC-IGF1R pathway promoted tumor metastasis. These data suggest that HULC may be a new epigenetic target for IGF1R axis-targeted therapeutic intervention. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

2. HULC targets the IGF1R–PI3K-AKT axis in trans to promote breast cancer metastasis and cisplatin resistance

Author

Lei Zhou, Hui Li, Tingge Sun, Xue Wen, Chao Niu, Min Li, Wei Li, Andrew R. Hoffman, Ji-Fan Hu, and Jiuwei Cui

Subjects
Cancer Research, Apoptosis, Chromatin, Receptor, IGF Type 1, Gene Expression Regulation, Neoplastic, Histones, Mice, Phosphatidylinositol 3-Kinases, Oncology, Cell Line, Tumor, Animals, RNA, Long Noncoding, Cisplatin, Insulin-Like Growth Factor I, Neoplasm Recurrence, Local, Proto-Oncogene Proteins c-akt, Cell Proliferation
Abstract

Insulin-like growth factor I receptor (IGF1R) is frequently upregulated in breast cancer. Due to its intrinsic tyrosine kinase activity, aberrant activation of the IGF1R signaling axis may enhance tumor cell proliferation and cancer stemness, causing tumor relapse, metastasis and resistance to chemotherapy. We utilized a chromatin RNA in situ reverse transcription (CRIST) approach to characterize molecular factors that regulate the IGF1R network. We identified lncRNA HULC (Highly Upregulated in Liver Cancer) as a key trans-regulator of IGF1R in breast cancer cells. Loss of HULC suppressed the expression of IGF1R and the activation of its downstream PI3K/AKT pathway, while HULC overexpression activated the axis in breast cancer cells. Using a transcription-associated trap (RAT) assay, we demonstrated that HULC functioned as a nuclear lncRNA and epigenetically activated IGF1R by directly binding to the intragenic regulatory elements of the gene, orchestrating intrachromosomal interactions, and promoting histone H3K9 acetylation. The activated HULC-IGF1R/PI3K/AKT pathway mediated tumor resistance to cisplatin through the increased expression of cancer stemness markers, including NANOG, SOX2, OCT4, CD44 and ALDH1A1. In immunodeficient mice, stimulation of the HULC-IGF1R pathway promoted tumor metastasis. These data suggest that HULC may be a new epigenetic target for IGF1R axis-targeted therapeutic intervention.

Published
2022

Catalog

Books, media, physical & digital resources
See catalog results