Table 1 Functional role of AMOT, AMOTL1, and AMOTL2 in different cancer types
From: The physiological role of Motin family and its dysregulation in tumorigenesis
| Â | Functions | Cancer type | Mechanism | References |
|---|---|---|---|---|
AMOT | Oncogene | Unknown | A DNA vaccine targeting AMOT inhibits angiogenesis and suppresses tumor growth. Therapeutic antibodies targeting AMOT inhibit angiogenesis in vivo. A vaccine targeting AMOT hampers tumor growth. sCD146 binds to Amot to stimulate a proangiogenic response. Tankyrase inhibitors antagonizes stabilize AMOT and result in constitutive activates of TEAD-dependent transcription and proliferation of human tumor cells | |
Breast cancer | AMOT is up-regulated and its expression links to the aggressive nature of breast cancer. It promotes breast cancer cell proliferation and invasion. AMOT increases the expression of YAP1 in the nucleoprotein. miR-205 inhibits the proliferation and invasion of breast cancer by regulating AMOT expression | |||
Sinonasal inverted papilloma | AMOT is over-expressed. It associates with progression and growth via promoting angiogenesis in sinonasal inverted papilloma | [83] | ||
Osteosarcoma | lncRNA SNHG12 promotes cell proliferation and migration by activating AMOT gene expression. Also, miR-497 inhibits cell proliferation, migration, and invasion by targeting AMOT | |||
Renal cell carcinoma | AMOT promotes cell proliferation by retaining the nuclear YAP1 | [98] | ||
Colon cancer | AMOT promotes the malignant potential of colon cancer cells by activating the YAP1-ERK/PI3Â K-AKT signaling pathway | [86] | ||
Tumor suppressor | Unknown | Form a TJ-associated protein complex with Merlin, Patj, and Pals1. AMOT inhibits MAPK signaling. AMOT inhibits YAP1 oncoprotein and restricts the activity of YAP1/TAZ. AMOT activates LATS2. Tankyrase inhibitors stabilize AMOT family proteins and suppress YAP1 oncogenic functions. Deubiquitylation of AMOT at lysine 496 by USP9x resulting in stabilization of AMOT and lower YAP1/TAZ activity | ||
Lung cancer | AMOT decreases lung cancer progression by sequestering oncogenic YAP1/TAZ and decreasing Cyr61 expression. Tankyrase inhibitor sensitizes lung cancer cells to endothelial growth factor receptor inhibition via stabilizing AMOT and inhibiting YAP1 signaling | |||
AMOT-p80 | Oncogene | Hemangioendothelioma | AMOT-p80 promotes angiogenesis by stimulating invasion and stabilizing established tubes | [77] |
Head and neck squamous cell carcinoma | High expression AMOT-p80 promotes cell proliferation and migration | [84] | ||
Prostate cancer | AMOT-p80 is a novel component of cadherin-11/β-catenin/p120 complex and promotes cell migration | [85] | ||
AMOT-p130 | Oncogene | Unknown | AMOT-p130 acts as a YAP1 cofactor, preventing YAP1 phosphorylation and augmenting its activity | [75] |
Tumor suppressor | Unknown | AMOT-p130 and AIP4 cooperatively reduces YAP1 and cell growth. AMOT-p130 selectively induced YAP1 phosphorylation and reduced transcription of connective tissue growth factor in an AIP4-dependent manner. AMOT-p130 decreased the growth of MDA-MB-468 breast cancer cells. AMOT-p130 (S175A)-expressing cells formed enlarged and poorly differentiated acini | ||
AMOTL1 | Oncogene | Breast cancer | AMOTL1 marginally expressed higher levels in tumor than normal tissues. AMOTL1 promotes breast cancer progression and is antagonized by Merlin. AMOTL1 is an essential effector of the N-cadherin mediated endothelial/pericyte junctional complex | |
Cervical cancer | MiR-124 represses vasculogenic mimicry and cell motility by targeting AMOTL1 | [100] | ||
Tumor suppressor | Unknown | AMOTL1 activates LATS2, inhibits YAP1, and restricts the activity of TAZ and YAP1. It inhibits YAP1′s nuclear translocation and pro-apoptotic function | ||
AMOTL2 | Oncogene | Unknown | AMOTL2 promotes cell migration and proliferation of angiogenic endothelial cells. It positively regulates MAPK/ERK activation | [40] |
Breast cancer | AMOTL2 marginally expressed higher in tumors. It disrupts apical–basal cell polarity and promotes tumor invasion | |||
Tumor suppressor | Unknown | AMOTL2 regulates YAP1 cytoplasm-to-nucleus translocation. AMOTL2 inhibits epithelial-mesenchymal transition. LATS2, AMOTL2, and YAP1 all localize to TJs, trigger LATS2 activation and growth inhibition in response to increased cell density. AMOTL2 mono-ubiquitination is required for YAP1 inhibition | ||
Glioblastoma | mTORC2/AMOTL2/YAP1 signaling cascade promotes glioblastoma growth and invasive characteristics. AMOTL2 upregulation inhibited YAP1-induced transcription, foci formation, growth, and metastatic properties both in vitro and in vivo | [76] |