The Drosophila Mst Ortholog, hippo, Restricts Growth and Cell Proliferation and Promotes Apoptosis

Harvey, Kieran F.; Pfleger, Cathie M.; Hariharan, Iswar K.

doi:10.1016/s0092-8674(03)00557-9

Cited by 858 publications

(806 citation statements)

References 40 publications

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“…Extensive research has led to the identification of the Hippo tumor suppressor pathway as a key regulator of organ size in Drosophila and mammals (Pan, 2010). By genetic mosaic screens, mutation of the first batch of Hippo pathway genes warts (wts) (Justice et al, 1995;Xu et al, 1995), hippo (hpo) (Harvey et al, 2003;Jia et al, 2003;Pantalacci et al, 2003;Udan et al, 2003;Wu et al, 2003), and salvador (sav) (Kango-Singh et al, 2002;Tapon et al, 2002) were found to dramatically promote tissue overgrowth and organ size enlargement. These genes belong to the hyperplastic group of Drosophila tumor suppressors wherein mutations of these genes result in robust tissue overgrowth without alterations of cell fate determination or cell polarity (Hariharan and Bilder, 2006).…”

Section: The Drosophila Hippo Pathwaymentioning

confidence: 99%

The Hippo pathway regulates stem cell proliferation, self-renewal, and differentiation

et al. 2012

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This pathway was first found to inhibit cell proliferation and promote apoptosis, therefore regulating cell number and organ size in both Drosophila and mammals. However, in several organs, disturbance of the pathway leads to specific expansion of the progenitor cell compartment and manipulation of the pathway in embryonic stem cells strongly affects their self-renewal and differentiation. In this review, we summarize current observations on roles of the Hippo pathway in different types of stem cells and discuss how these findings changed our view on the Hippo pathway in organ development and tumorigenesis.

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Section: The Drosophila Hippo Pathwaymentioning

confidence: 99%

The Hippo pathway regulates stem cell proliferation, self-renewal, and differentiation

et al. 2012

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“…13 Based on its proposed function in apoptosis, Mst1 might play a tumor suppressor role in human cancers as has been suggested for its Drosophila homologs. [14][15][16][17] Nevertheless, there is no report on the biological significance of Mst1 expression in primary human cancer cells. Herein, we report the prognostic significance of cytoplasmic and nuclear expression of Mst1 in a large group of patients with colorectal cancer.…”

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confidence: 99%

Prognostic significance of mammalian sterile20-like kinase 1 in colorectal cancer

et al. 2007

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Mammalian Sterile20-like kinase 1 (Mst1) is a member of the yeast Ste20-related kinase family known to be involved in the process of apoptosis initiated by a variety of stimuli. The aim of this study was to determine the prognostic significance of Mst1 expression in colorectal cancer. A series of 1197 mismatch-repair-proficient colorectal cancers retrieved from a tissue microarray were randomized into two study groups. On the first group (n ¼ 599) receiver operating characteristic curves were used to determine the most clinically useful cutoffs to describe Mst1 expression with respect to T stage, N stage, tumor grade, vascular invasion and overall survival. The association of Mst1 expression and each outcome was immunohistochemically evaluated on the second study group (n ¼ 598) as well as on a third study group comprising 141 mismatch-repair-deficient colorectal cancers. A univariate analysis in the second study group showed that loss of cytoplasmic Mst1 was associated with higher T stage (P ¼ 0.001), higher N stage (P ¼ 0.029), vascular invasion (P ¼ 0.017) and overall survival (P ¼ 0.014). Nuclear Mst1 expression was not significantly associated with N stage, T stage or vascular invasion but was associated with tumor grade. In mismatch-repair-deficient colorectal cancers, loss of cytoplasmic Mst1 was associated with higher N stage (P ¼ 0.019) and shortened survival (P ¼ 0.0001). In a multivariate analysis, loss of cytoplasmic Mst1 was an independent adverse prognostic factor in this group of patients. Methylation analysis on 32 cases showed that the loss of cytoplasmic Mst1 expression is not likely due to promoter methylation. In summary, loss of cytoplasmic Mst1 expression is a marker of tumor progression in mismatchrepair-proficient as well as mismatch-repair-deficient colorectal cancers. These results are suggestive of a tumor suppressor role for Mst1 in human colorectal cancer.

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“…In fact, phosphorylation by the Hpo/Sav/ Wts pathway seems to promote the degradation of DIAP1, although the phosphorylated residues have not been identified. 13,14 Cells also regulate the activity of IAPs post-translationally through proteolytic cleavage. As with phosphorylation, the biological consequence of IAP cleavage varies.…”

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confidence: 99%

XLX is an IAP family member regulated by phosphorylation during meiosis

Greenwood

Gautier

2006

Cell Death Differ

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The balance between proliferation and cell death is critical for embryonic development and adult tissue homeostasis. Within an individual cell, coordination of these pathways is aided by direct communication between cell cycle factors and molecules that regulate apoptosis. Here, we show that XLX, a Xenopus laevis inhibitor of apoptosis (IAP) family member, exhibits characteristics typical of an IAP, such as caspase inhibition and autoubiquitylation. However, unlike other IAPs described thus far, we found that XLX is phosphorylated during meiosis by protein kinases that belong to the MAPK and MPF pathways. Finally, we show that caspase-dependent cleavage of XLX is altered when XLX is phosphorylated. In addition to furthering our understanding of the post-translational regulation of an IAP, these findings reveal a novel link between cell cycle-regulated protein kinases and a component potentially involved in apoptosis.

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The Drosophila Mst Ortholog, hippo, Restricts Growth and Cell Proliferation and Promotes Apoptosis

Cited by 858 publications

References 40 publications

The Hippo pathway regulates stem cell proliferation, self-renewal, and differentiation

The Hippo pathway regulates stem cell proliferation, self-renewal, and differentiation

Prognostic significance of mammalian sterile20-like kinase 1 in colorectal cancer

XLX is an IAP family member regulated by phosphorylation during meiosis

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