Anaplastic Lymphoma Kinase Spares Organ Growth during Nutrient Restriction in Drosophila
نویسندگان
چکیده
Developing animals survive periods of starvation by protecting the growth of critical organs at the expense of other tissues. Here, we use Drosophila to explore the as yet unknown mechanisms regulating this privileged tissue growth. As in mammals, we observe in Drosophila that the CNS is more highly spared than other tissues during nutrient restriction (NR). We demonstrate that anaplastic lymphoma kinase (Alk) efficiently protects neural progenitor (neuroblast) growth against reductions in amino acids and insulin-like peptides during NR via two mechanisms. First, Alk suppresses the growth requirement for amino acid sensing via Slimfast/Rheb/TOR complex 1. And second, Alk, rather than insulin-like receptor, primarily activates PI3-kinase. Alk maintains PI3-kinase signaling during NR as its ligand, Jelly belly (Jeb), is constitutively expressed from a glial cell niche surrounding neuroblasts. Together, these findings identify a brain-sparing mechanism that shares some regulatory features with the starvation-resistant growth programs of mammalian tumors.
منابع مشابه
Expression of Anaplastic Lymphoma Kinase Protein in Human Breast Cancer
Background & Objectives: Anaplastic lymphoma Kinase (ALK) is a receptor tyrosine kinase involved in the genesis of several human cancers. ALK was initially identified because of its involvement in anaplastic large cell lymphoma (ALCL). ALK is believed to foster tumorigenesis following activation by autocrine and/or paracrine growth loops. Studies reveal that the presence of anti-ALK antibodies ...
متن کاملAnaplastic Large Cell Lymphoma Associated with Breast Implant: A Case Report
Primary breast lymphoma represents less than 1% of all primary breast malignancies and most primary breast lymphomas are of B-Cell origin. The association of anaplastic lymphoma kinase (ALK) negative anaplastic large cell lymphoma (ALCL), a very rare form of primary breast lymphoma, with silicone-filled breast implants has been suggested and several case reports supported this proposal, especia...
متن کاملInflammatory Pseudotumor Of The Orbit: A Histopathologic And Immunohistochemical Study Of 32 Cases
Background and Objective: Inflammatory pseudotumor is a lesion composed of proliferating spindle cells with mixed inflammatory infiltrates. Some authors have proposed the name inflammatory myofibroblastic tumor as a proper descriptive term rather than the vague inflammatory pseudotumor. The aim of this study was to verify the myofibroblastic origin of spindle cells in idiopathic orbital inf...
متن کاملPrivileged Signaling for Brain Growth
When developing animals encounter nutrient restriction, most tissues stop growing. Some vital tissues, however, such as the brain, continue to grow. Now, Cheng et al. (2011) identify Alk as the kinase that allows the Drosophila brain to continue growing during nutrient restriction by bypassing the requirements for insulin receptor and TOR activation.
متن کاملBrigatinib, an anaplastic lymphoma kinase inhibitor, abrogates activity and growth in ALK-positive neuroblastoma cells, Drosophila and mice
Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor which has been implicated in numerous solid and hematologic cancers. ALK mutations are reported in about 5-7% of neuroblastoma cases but the ALK-positive percentage increases significantly in the relapsed patient population. Crizotinib, the first clinically approved ALK inhibitor for the treatment of ALK-positive lung cancer has had...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Cell
دوره 146 شماره
صفحات -
تاریخ انتشار 2011