Extravasation and metastatic progression are two main reasons behind the high mortality rate associated with @entity5 . The metastatic potential of @entity5 cells depends on a plethora of metabolic challenges prevailing in the @entity5 microenvironment. To achieve higher proliferative rates, @entity5 cells reprogram their metabolism, increasing glycolysis and biosynthetic activities. Just why this metabolic reprogramming predisposes cells towards increased oncogenesis remains elusive. The accumulation of myriad oncolipids in the @entity5 microenvironment has been shown to promote the invasiveness of @entity5 cells, with @entity4990 ( @entity4991 ) being one such critical factor enriched in @entity43 ( @entity43 ) @entity1 . Cellular bioenergetic studies confirm that oxidative phosphorylation is suppressed and glycolysis is increased with long exposure to @entity4991 in @entity43 cells compared to non-transformed epithelial cells. We sought to uncover the regulatory complexity underlying this oncolipid-induced metabolic perturbation. Gene regulatory networking using RNA-Seq analysis identified the oncogene @entity12136 as a critical mediator of the @entity4991 -induced metabolic alterations for the maintenance of invasive phenotype. Moreover, @entity42659 -receptor-specific PI3K-AKT signaling induces @entity12136 and its target matrix metalloproteases. Abrogation of @entity12136 restores cellular bioenergetics towards increased oxidative phosphorylation and reduced glycolysis, and this effect was reversed by the presence of @entity4991 . Furthermore, the bioenergetic status of @entity4991 -treated @entity43 cells mimics @entity519 through induction of @entity7738 , which was found to transactivate @entity12136 . Studies in @entity5 generated in syngeneic @entity19 corroborated the in vitro findings. Thus, our study highlights the phenotypic changes induced by the pro-metastatic factor @entity12136 in @entity43 cells. The relationship between enhanced invasiveness and metabolic plasticity further illustrates a critical role of metabolic adaptation of @entity5 cells as a driver of @entity5 progression. These findings reveal oncolipid-induced metabolic predisposition as a new mechanism of tumorigenesis and propose metabolic inhibitors as a potential approach for future management of aggressive @entity43 . This article is protected by copyright. All rights reserved.

Gene regulatory networking reveals the molecular cue to XXXX -induced metabolic adaptations in @entity43 cells.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity43 :: ('MESH:D010051', 'Disease') :: ['OC', 'ovarian cancer'] @entity7738 :: ('3091', 'Gene') :: ['HIF-1a'] @entity4990 :: ('MESH:C032881', 'Chemical') :: ['lysophosphatidic acid'] @entity12136 :: ('2113', 'Gene') :: ['ets-1', 'ETS-1'] @entity4991 :: ('CHEBI:52288', 'Chemical') :: ['LPA'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'primary tumors', 'cancer'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity519 :: ('MESH:D000860', 'Disease') :: ['hypoxia'] @entity42659 :: ('9170', 'Gene') :: ['LPAR2']
@entity4990 :: (MESH:C032881,Chemical) :: ['lysophosphatidic acid']
