Lineage-specific intolerance to oncogenic drivers restricts histological transformation

Abstract

Lung adenocarcinoma (LUAD) and small cell lung cancer (SCLC) are thought to originate from different epithelial cell types in the lung. Intriguingly, LUAD can histologically transform into SCLC after treatment with targeted therapies. In this study, we designed models to follow the conversion of LUAD to SCLC and found that the barrier to histological transformation converges on tolerance to Myc, which we implicate as a lineage-specific driver of the pulmonary neuroendocrine cell. Histological transformations are frequently accompanied by activation of the Akt pathway. Manipulating this pathway permitted tolerance to Myc as an oncogenic driver, producing rare, stem-like cells that transcriptionally resemble the pulmonary basal lineage. These findings suggest that histological transformation may require the plasticity inherent to the basal stem cell, enabling tolerance to previously incompatible oncogenic driver programs.

Albumin-Based MUC13 Peptide Nanomedicine Suppresses Liver Cancer Stem Cells via JNK-ERK Signaling Pathway-Mediated Autophagy Inhibition

“…Given that cancer stem cells are regarded as the workhorse of tumor-initiating and its stemness contributes to the indefinite proliferation and recurrence of tumor, it is of vital importance to inhibit the stemness of cancer cells. − Therefore, having successfully constructed the P3@HSA nanomedicine, we next moved to the assessments of the ability for eliminating the stemness property of LCSCs. Since HCCLM3 cells are enriched with stem-like cancer cells and have higher metastatic potential than other liver cancer cell lines, , we isolated LCSCs from HCCLM3 cells using the microsphere culture method for further experiments .…”