Altogether, we report for the first time that the expression of the human ALK-F1174L mutation in NCCs during embryonic development profoundly disturbs early sympathetic progenitor differentiation, in addition to increasing their proliferation, both mechanisms being potential crucial events in NB oncogenesis.
A kinome-wide screen using a NanoLuc LATS luminescent biosensor identifies ALK as a novel regulator of the Hippo pathway in tumorigenesis and immune evasion.
To determine the oncogenic potential of increased ALK activity in thyroid carcinogenesis <i>in vivo</i>, we studied mice with thyrocyte-specific expression of a constitutively active ALK mutant.
Since most cases are in children under the age of 2, understanding the role and regulation of ALK during neural crest development is an important goal in addressing neuroblastoma tumorigenesis.
Moreover, identification of ALK-mediated molecular pathway(s) related to GBM carcinogenesis/ pathology and putative therapy resistance is of high priority and warrants further exploitation.
ALK is rearranged in approximately 80% of systemic ALCL cases with one of its partner genes, most commonly <i>NPM1</i>, and is associated with favorable prognosis, whereas systemic ALK# ALCL shows heterogeneous clinical, phenotypical, and genetic features, underlining the different oncogenesis between these two entities.
Anaplastic lymphoma kinase (ALK) gene activation is involved in the carcinogenesis process of several human cancers such as anaplastic large cell lymphoma, lung cancer, inflammatory myofibroblastic tumors and neuroblastoma, as a consequence of fusion with other oncogenes (NPM, EML4, TIM, etc) or gene amplification, mutation or protein overexpression.
In our study, ALK rearrangements are uncommon in both CBN and DPN, making ALK an unlikely driver in tumorigenesis and classification of these melanocytic variants.
Anaplastic lymphoma kinase (<i>ALK</i>) gene rearrangements have been identified in lung cancer at 3-7% frequency, thus representing an important subset of genetic lesions that drive oncogenesis in this disease.
Dysregulation of miRNA expression and regulation has been shown to affect several signaling pathways in ALKcarcinogenesis and control tumor growth, both in cell lines and mouse models.
These include epidermal growth factor receptor mutations and anaplastic lymphoma kinase translocations, which are responsible for both carcinogenesis and cancer growth and survival.
Recently, the deregulated expression of full-length ALK has been observed in some primary solid tumors, but little is known about its involvement in the tumorigenesis of uterine carcinosarcomas (UCSs).
Moreover, a high level of ALK protein has been associated with metastatic NB cases and with a worse prognosis, suggesting that also ALK overexpression is involved in NB tumorigenesis.
This review summarizes the current understanding of ALK-driven cancers from the oncogenesis and mutation frequency by The Cancer Genome Atlas database through the diagnostic approach, to an updated portrait of available tyrosine kinase inhibitors, considering their effectiveness in cancer treatment, the molecular reasons of therapeutic failure, and the actual and future ways to overcome resistances.
The discovery of activating kinase domain mutations of the full-length ALK receptor as the major cause of hereditary neuroblastoma, and that somatically acquired mutations and amplification events often drive the malignant process in a subset of sporadic tumors, has established ALK as a tractable molecular target across histologically diverse tumors in which ALK is a critical mediator of oncogenesis.
SKP2 inhibition supports a function for SKP2 in the maintained neuroblast proliferation downstream of MYCN/ALK, which may represent an early step toward tumorigenesis.
The anaplastic lymphoma kinase (ALK) protein drives tumorigenesis in subsets of several tumors through chromosomal rearrangements that express and activate its C-terminal kinase domain.