CEACAM1 promotes melanoma cell growth through Sox-2.

The prognostic value of the carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) in melanoma was demonstrated more than a decade ago as superior to Breslow score. We have previously shown that intercellular homophilic CEACAM1 interactions protect melanoma cells from lymphocyte-mediated elimination. Here, we study the direct effects of CEACAM1 on melanoma cell biology.

Novel anti-melanoma immunotherapies: disarming tumor escape mechanisms.

The immune system fights cancer and sometimes temporarily eliminates it or reaches an equilibrium stage of tumor growth. However, continuous immunological pressure also selects poorly immunogenic tumor variants that eventually escape the immune control system. Here, we focus on metastatic melanoma, a highly immunogenic tumor, and on anti-melanoma immunotherapies, which recently, especially following the FDA approval of Ipilimumab, gained interest from drug development companies.

Novel immunotherapy for malignant melanoma with a monoclonal antibody that blocks CEACAM1 homophilic interactions.

CEACAM1 (biliary glycoprotein-1, CD66a) was reported as a strong clinical predictor of poor prognosis in melanoma. We have previously identified CEACAM1 as a tumor escape mechanism from cytotoxic lymphocytes. Here, we present substantial evidence in vitro and in vivo that blocking of CEACAM1 function with a novel monoclonal antibody (MRG1) is a promising strategy for cancer immunotherapy.

CXCR1 as a novel target for directing reactive T cells toward melanoma: implications for adoptive cell transfer immunotherapy.

Adoptive cell transfer therapy with reactive T cells is one of the most promising immunotherapeutic modalities for metastatic melanoma patients. Homing of the transferred T cells to all tumor sites in sufficient numbers is of great importance. Here, we seek to exploit endogenous chemotactic signals in order to manipulate and enhance the directional trafficking of transferred T cells toward melanoma.

Serum CEACAM1 Correlates with Disease Progression and Survival in Malignant Melanoma Patients.

The search for melanoma biomarkers is crucial, as the incidence of melanoma continues to rise. We have previously demonstrated that serum CEACAM1 (sCEACAM1) is secreted from melanoma cells and correlates with disease progression in metastatic melanoma patients. Here, we have used a different cohort of melanoma patients with regional or metastatic disease (N = 49), treated with autologous vaccination.

Ndel1 palmitoylation: a new mean to regulate cytoplasmic dynein activity.

Regulated activity of the retrograde molecular motor, cytoplasmic dynein, is crucial for multiple biological activities, and failure to regulate this activity can result in neuronal migration retardation or neuronal degeneration. The activity of dynein is controlled by the LIS1-Ndel1-Nde1 protein complex that participates in intracellular transport, mitosis, and neuronal migration. These biological processes are subject to tight multilevel modes of regulation.

Systemic dysregulation of CEACAM1 in melanoma patients.

It was previously shown that CEACAM1 on melanoma cells strongly predicts poor outcome. Here, we show a statistically significant increase of serum CEACAM1 in 64 active melanoma patients, as compared to 48 patients with no evidence of disease and 37 healthy donors. Among active patients, higher serum CEACAM1 correlated with LDH values and with decreased survival.

Accurate balance of the polarity kinase MARK2/Par-1 is required for proper cortical neuronal migration.

Radial neuronal migration is key in structuring the layered cortex. Here we studied the role of MARK2/Par-1 in this process. The dual name stands for the MAP/microtubule affinity-regulating kinase 2 (MARK2) and the known polarity kinase 1 (Par-1).

Lissencephaly 1 linking to multiple diseases: mental retardation, neurodegeneration, schizophrenia, male sterility, and more.

Lissencephaly 1 (LIS1) was the first gene implicated in the pathogenesis of type-1 lissencephaly. More than a decade of research by multiple laboratories has revealed that LIS1 is a key node protein, which participates in several pathways, including association with the molecular motor cytoplasmic dynein, the reelin signaling pathway, and the platelet-activating factor pathway. Mutations in LIS1-interacting proteins, either in human, or in mouse models has suggested that LIS1 might play a role in the pathogenesis of numerous diseases such as male sterility, schizophrenia, neuronal degeneration, and viral infections.

Site-specific dephosphorylation of doublecortin (DCX) by protein phosphatase 1 (PP1).

Mutations in doublecortin (DCX) cause X-linked lissencephaly ("smooth brain") and double cortex syndrome in humans. DCX is highly phosphorylated in migrating neurons. Here, we demonstrate that dephosphorylation of specific sites phosphorylated by JNK is mediated by Neurabin II, which recruits the phosphatase PP1.

DCX's phosphorylation by not just another kinase (JNK).

The mammalian cortex is generally subdivided into six organized layers, which are formed during development in an organized fashion. This organized cortical layering is disrupted in case of mutations in the doublecortin (DCX) gene. DCX is a Microtubule Associated Protein (MAP).

DCX, a new mediator of the JNK pathway.

Mutations in the X-linked gene DCX result in lissencephaly in males, and abnormal neuronal positioning in females, suggesting a role for this gene product during neuronal migration. In spite of several known protein interactions, the involvement of DCX in a signaling pathway is still elusive. Here we demonstrate that DCX is a substrate of JNK and interacts with both c-Jun N-terminal kinase (JNK) and JNK interacting protein (JIP).