Fig. 2: Crosstalk of the Hippo pathway with other signaling networks. | Cell Death & Disease

Fig. 2: Crosstalk of the Hippo pathway with other signaling networks.

From: Hippo pathway dysregulation in gastric cancer: from Helicobacter pylori infection to tumor promotion and progression

Fig. 2

A The functional connection between mTOR (regulating cell size) and Hippo (regulating proliferation) pathways is essential for the proper organ development. At the basis of this crosstalk, YAP can downregulate PTEN (Phosphatase and tensin homolog), whereas LATS1/2 (Large tumor suppressor kinase 1/2) can phosphorylate Raptor, resulting in inhibition of mTOR signaling. B Under energy stress condition, the AMP-activated protein kinase (AMPK) phosphorylates and stabilizes AMOTL1 (Angiomotin Like 1), together with inducing both direct and LATS-mediated YAP phosphorylation, leading to YAP inhibition. C In conditions of high cell density, the Hippo pathway is activated and cytoplasmic YAP/TAZ retain TGFβ (transforming growth factor β)-activated SMAD family members 2/3-4 (SMAD 2/3-4) in the cytoplasm. At low cell density, YAP/TAZ and SMAD 2/3-4 translocate to the nucleus to cooperatively induce transcription. D YAP and TAZ are members of β-catenin destruction complex, responsible for β-catenin inactivation. Upon activation of the Wnt pathway, YAP/TAZ and β-catenin enter the nucleus and synergistically induce Wnt and TEAD (TEA Domain transcription factor) target genes. Moreover, by complexing with TBX5 (T-box transcription factor 5), they induce anti-apoptotic genes.

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