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Transcription factor EB (TFEB), a member of the MiT family, is dysregulated in different cancers and exerts specific biological functions within the tumor microenvironment. Downregulation of TFEB induces macrophage polarization in the TME and promotes tumor progression. However, the biological role and clinical significance of TFEB in prostate cancer (PCa) remain unknown. This study aimed to identify the role of TFEB in PCa and its potential clinical value. We explored TFEB expression in PCa using public databases and verified its prognostic value using immunohistochemistry in PCa tissue samples. The results revealed that TFEB expression was up-regulated in PCa tissues and was associated with cancer metastasis. Next, overexpression of TFEB promoted PCa cell malignant behavior in in vivo and in vitro experiments. RNA-sequencing and bioinformatics analysis showed high expression of TFEB promoted lysosomal biogenesis and knockdown of TFEB expression decreased the number of lysosomes. Furthermore, the ATP-binding cassette transporter A2 (ABCA2) was identified as a target gene of TFEB, which was verified using the cleavage under targets and release using nuclease (CUT&RUN) assay and qRT-PCR. Silencing of ABCA2 reduced lysosomal biogenesis and decreased matrix metalloproteinases expression, which reduced PCa cell invasion and migration in the tumor microenvironment. Our study suggests that TFEB promotes PCa progression by regulating ABCA2 through lysosomal biogenesis and may serve as a prognostic factor or as a potential therapeutic target of PCa. [ABSTRACT FROM AUTHOR]

TFEB, ABCA2, prostate cancer, tumor microenvironment, lysosomal biogenesis, biochemical recurrence, metastasis Keywords: TFEB; ABCA2; prostate cancer; tumor microenvironment; lysosomal biogenesis; biochemical recurrence; metastasis EN TFEB ABCA2 prostate cancer tumor microenvironment lysosomal biogenesis biochemical recurrence metastasis 1 3 3 09/02/21 20210830 NES 210830 In the original article, there was a mistake in B I Figure 6 i b as published. [Extracted from the article]

Diagnosis of the presence of tumors and subsequent prognosis based on tumor microenvironment becomes more clinically practical because tumor-adjacent tissues are easy to collect and they are more genetically homogeneous. The purpose of this study was to identify new prognostic markers in prostate stroma that are near the tumor. We have demonstrated the prognostic features of FGFR1, FRS2, S6K1, LDHB, MYPT1, and P-LDHA in prostate tumors using tissue microarrays (TMAs) which consist of 241 patient samples from Massachusetts General Hospital (MGH). In this study, we investigated these six markers in the tumor microenvironment using an Aperio Imagescope system in the same TMAs. The joint prognostic power of markers was further evaluated and classified using a new algorithm named Weighted Dichotomizing. The classifier was verified via rigorous 10-fold cross validation. Statistical analysis of the protein expression indicated that in tumor-adjacent stroma FGFR1 and MYPT1 were significantly correlated with patient outcomes and LDHB showed the outcome-association tendency. More interestingly, these correlations were completely opposite regarding tumor tissue as previously reported. The results suggest that prognostic testing should utilize either tumor-enriched tissue or stroma with distinct signature profiles rather than using mixture of both tissue types. The new classifier based on stroma tissue has potential value in the clinical management of prostate cancer patients. [ABSTRACT FROM AUTHOR]