Abstract
The Hippo signaling pathway is a highly conserved pathway controlling organ size, cell proliferation, apoptosis and other biological functions. Recent studies have shown that Hippo signaling pathway also plays important roles in cancer initiation and progression. However, a database offering multi-omics analyses and visualization of Hippo pathway genes in cancer, as well as comprehensive Hippo regulatory relationships is still lacking. To fill this gap, we constructed the Regulation of the Hippo Pathway in Cancer Genome (RHPCG) database. Currently, RHPCG focuses on analyzing the 21 core Hippo-protein-encoding genes in over 10 000 patients across 33 TCGA (The Cancer Genome Atlas) cancer types at the levels of genomic, epigenomic and transcriptomic landscape. Concurrently, RHPCG provides in its motif section 11 regulatory motif types associated with 21 core Hippo pathway genes containing 180 miRNAs, 6182 lncRNAs, 728 circRNAs and 335 protein coding genes. Thus, RHPCG is a powerful tool that could help researchers understand gene alterations and regulatory mechanisms in the Hippo signaling pathway in cancer.
Highlights
The Hippo signaling pathway is a highly conserved pathway initially discovered in Drosophila [1] and consists of a group of kinases, including among others the serine/ threonine STE20-like protein kinases (serine/threonine– protein kinase 3 (STK3), known as MST2, and serine/threonine-protein kinase 4 (STK4), known as MST1), the large tumor suppressors (large tumor suppressor kinase 1 (LATS1) and 2 (LATS2)), and the MOB kinase activators (MOB1A/MOB1B) [2]
When the Hippo signaling pathway is inhibited, the YAP1/transcriptional coactivator with PDZ-binding motif (TAZ) coactivators go into the nucleus and bind to TEADs to start the downstream transcription process, which induces epithelial-mesenchymal transition (EMT) and cell proliferation (Figure 2A)
Dysregulation of the Hippo signaling pathway was found in several types of cancers, suggesting that the Hippo signaling pathway might constitute an effective target for cancer treatment [11]
Summary
The Hippo signaling pathway is a highly conserved pathway initially discovered in Drosophila [1] and consists of a group of kinases, including among others the serine/ threonine STE20-like protein kinases (serine/threonine– protein kinase 3 (STK3), known as MST2, and serine/threonine-protein kinase 4 (STK4), known as MST1), the large tumor suppressors (large tumor suppressor kinase 1 (LATS1) and 2 (LATS2)), and the MOB kinase activators (MOB1A/MOB1B) [2] These kinases directly or indirectly phosphorylate the key function effectors, yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), blocking the transcription of downstream target genes. Despite the accumulated knowledge, a database systematically analyzing and presenting the deregulation of Hippo-signaling-pathway genes and its effects in pan-cancer at the levels of genome, epigenome, transcriptome and proteome is still lacking
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