Open AccessSox2 is necessary for androgen ablation-induced neuroendocrine differentiation from Pten null Sca-1+ prostate luminal cells
Author(s) -
OhJoon Kwon,
Li Zhang,
Dongyu Jia,
Xin Li
Publication year - 2020
Publication title -
oncogene
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.395
H-Index - 342
eISSN - 1476-5594
pISSN - 0950-9232
DOI - 10.1038/s41388-020-01526-2
Subject(s) - biology , neuroendocrine differentiation , sox2 , prostate cancer , pten , cancer research , prostate , androgen , androgen receptor , neuroendocrine cell , somatic cell , adenocarcinoma , carcinogenesis , medicine , cancer , endocrinology , pi3k/akt/mtor pathway , microbiology and biotechnology , immunology , genetics , hormone , gene , signal transduction , transcription factor , immunohistochemistry
Prostate adenocarcinoma undergoes neuroendocrine differentiation to acquire resistance toward antihormonal therapies. The underlying mechanisms have been investigated extensively, among which Sox2 has been shown to play a critical role. However, genetic evidence in mouse models for prostate cancer to support the crucial role of Sox2 is missing. The adult mouse prostate luminal cells contain both castration-resistant Sox2-expressing Sca-1 + cells and castration-responsive Sca-1 - cells. We show that both types of the luminal cell are susceptible to oncogenic transformation induced by loss of function of the tumor suppressor Pten. The tumors derived from the Sca-1 + cells are castration resistant and are more inclined to develop castration-induced neuroendocrine differentiation. Genetic ablation of Sox2 suppresses neuroendocrine differentiation but does not impact the castration-resistant property. This study provides direct genetic evidence that Sox2 is necessary for androgen ablation-induced neuroendocrine differentiation of Pten null prostate adenocarcinoma, corroborates that the lineage status of the prostate cancer cells is a determinant for its propensity to exhibit lineage plasticity, and supports that the intrinsic features of cell-of-origin for prostate cancers can dictate their clinical behaviors.