Angiomotin family proteins are novel activators of the LATS2 kinase tumor suppressor

Paramasivam, M.; Sarkeshik, Ali; Yates, John R.; Fernandes, Maria J.; McCollum, Dannel

doi:10.1091/mbc.e11-04-0300

Cited by 197 publications

(195 citation statements)

References 38 publications

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“…Amot, AmotL1 and AmotL2 all contain WW-binding motifs that interact with the Yap1 oncoprotein, which is then retained in the cellular junctions [47][48][49] . This suggests a tumour-suppressive role of p100 AmotL2.…”

Section: Resultsmentioning

confidence: 99%

AmotL2 disrupts apical–basal cell polarity and promotes tumour invasion

et al. 2014

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The establishment and maintenance of apical-basal cell polarity is essential for the functionality of glandular epithelia. Cell polarity is often lost in advanced tumours correlating with acquisition of invasive and malignant properties. Despite extensive knowledge regarding the formation and maintenance of polarity, the mechanisms that deregulate polarity in metastasizing cells remain to be fully characterized. Here we show that AmotL2 expression correlates with loss of tissue architecture in tumours from human breast and colon cancer patients. We further show that hypoxic stress results in activation of c-Fos-dependent expression of AmotL2 leading to loss of polarity. c-Fos/hypoxia-induced p60 AmotL2 interacts with the Crb3 and Par3 polarity complexes retaining them in large vesicles and preventing them from reaching the apical membrane. The resulting loss of polarity potentiates the response to invasive cues in vitro and in vivo in mice. These data provide a molecular mechanism how hypoxic stress deregulates cell polarity during tumour progression.

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Section: Resultsmentioning

confidence: 99%

AmotL2 disrupts apical–basal cell polarity and promotes tumour invasion

et al. 2014

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“…Motin proteins have been reported to regulate Hippo signaling pathway by activating LATS and trapping YAP and TAZ in the cytoplasm (21,23,31,46). On the other hand, Hippo signaling has been found to suppress Wnt/␤-catenin signal transduction via distinct mechanisms (47)(48)(49).…”

Section: Discussionmentioning

confidence: 99%

“…These proteins have been demonstrated to play important roles in angiogenesis, cell mobility, cell polarity, and cell-cell junctions by regulating distinct signaling pathways (15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Interestingly, it appears that each Motin family member in human and mice has two isoforms, long and short isoform (14), which function differently in physiological processes (17,(25)(26)(27)(28).…”

mentioning

confidence: 99%

The Amotl2 Gene Inhibits Wnt/β-Catenin Signaling and Regulates Embryonic Development in Zebrafish

Wang

Zhang

et al. 2012

Journal of Biological Chemistry

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“…Overexpression of Merlin promotes phosphorylation and nuclear extrusion of YAP, a downstream target of the Hippo kinase cascade [33,94], which functions as a co-activator of TEAD transcription factors (Fig 3B; [97,98]). By contrast, silencing of Merlin induces TEAD-dependent transcription [92].…”

Section: Activation Of the Hippo Pathwaymentioning

confidence: 99%

Merlin: a tumour suppressor with functions at the cell cortex and in the nucleus

et al. 2012

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Inhibition of proliferation by cell-to-cell contact is essential for tissue organization, and its disruption contributes to tumorigenesis. The FERM domain protein Merlin, encoded by the NF2 tumour suppressor gene, is an important mediator of contact inhibition. Merlin was thought to inhibit mitogenic signalling and activate the Hippo pathway by interacting with diverse target-effectors at or near the plasma membrane. However, recent studies highlight that Merlin pleiotropically affects signalling by migrating into the nucleus and inducing a growth-suppressive programme of gene expression through its direct inhibition of the CRL4 DCAF1 E3 ubiquitin ligase. In addition, Merlin promotes the establishment of epithelial adhesion and polarity by recruiting Par3 and aPKC to E-cadherin-dependent junctions, and by ensuring the assembly of tight junctions. These recent advances suggest that Merlin acts at the cell cortex and in the nucleus in a similar, albeit antithetic, manner to the oncogene β-catenin.

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Angiomotin family proteins are novel activators of the LATS2 kinase tumor suppressor

Cited by 197 publications

References 38 publications

AmotL2 disrupts apical–basal cell polarity and promotes tumour invasion

AmotL2 disrupts apical–basal cell polarity and promotes tumour invasion

The Amotl2 Gene Inhibits Wnt/β-Catenin Signaling and Regulates Embryonic Development in Zebrafish

Merlin: a tumour suppressor with functions at the cell cortex and in the nucleus

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