ALK upregulates POSTN and WNT signaling to drive neuroblastoma

ALK upregulates POSTN and WNT signaling to drive neuroblastoma

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Summary: Neuroblastoma is the most common extracranial solid tumor of childhood.While MYCN and mutant anaplastic lymphoma kinase (ALKF1174L) cooperate in tumorigenesis, how ALK contributes to tumor formation remains unclear.Here, we used a human stem cell-based model cocktail tree for sale of neuroblastoma.Mis-expression of ALKF1174L and MYCN resulted in shorter latency compared to MYCN alone.

MYCN tumors resembled adrenergic, while ALK/MYCN tumors resembled mesenchymal, neuroblastoma.Transcriptomic analysis revealed enrichment in focal adhesion signaling, particularly the extracellular matrix genes POSTN and FN1 in ALK/MYCN tumors.Patients with ALK-mutant tumors similarly demonstrated elevated levels of POSTN and iphone 13 price ohio FN1.Knockdown of POSTN, but not FN1, delayed adhesion and suppressed proliferation of ALK/MYCN tumors.

Furthermore, loss of POSTN reduced ALK-dependent activation of WNT signaling.Reciprocally, inhibition of the WNT pathway reduced expression of POSTN and growth of ALK/MYCN tumor cells.Thus, ALK drives neuroblastoma in part through a feedforward loop between POSTN and WNT signaling.