978: A multimarker panel for circulating tumor cells detection predicts patient outcome and therapy response in metastatic colorectal cancer

Barbazán, Jorge; Muinelo-Romay, L.; Vieito, María; Candamio, Sonia; Díaz‐López, Antonio; Cano, A.; Gómez-Tato, Antonio; Cal, Mariela; Abal, Mariana; López‐López, Rafael

doi:10.1016/s0959-8049(14)50867-2

Cited by 1 publication

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“…For instance, MUC2 overexpression correlates with resistance to concurrent chemoradiotherapy in colorectal cancer and has been linked to poor prognosis [116,117]. VIL1 has been identified as a novel marker for poor response to radiation treatment for patients with cervical adenocarcinoma [118,119]. SNGH25, a long noncoding RNA, is associated with poor prognosis in various cancers such as glioblastoma, endometrial cancer, and prostate cancer [120][121][122].…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoid Receptor Regulates and Interacts with LEDGF/p75 to Promote Docetaxel Resistance in Prostate Cancer Cells

Sanchez-Hernández

Ochoa

Suzuki

et al. 2023

Cells

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Patients with advanced prostate cancer (PCa) invariably develop resistance to anti-androgen therapy and taxane-based chemotherapy. Glucocorticoid receptor (GR) has been implicated in PCa therapy resistance; however, the mechanisms underlying GR-mediated chemoresistance remain unclear. Lens epithelium-derived growth factor p75 (LEDGF/p75, also known as PSIP1 and DFS70) is a glucocorticoid-induced transcription co-activator implicated in cancer chemoresistance. We investigated the contribution of the GR–LEDGF/p75 axis to docetaxel (DTX)-resistance in PCa cells. GR silencing in DTX-sensitive and -resistant PCa cells decreased LEDGF/p75 expression, and GR upregulation in enzalutamide-resistant cells correlated with increased LEDGF/p75 expression. ChIP-sequencing revealed GR binding sites in the LEDGF/p75 promoter. STRING protein–protein interaction analysis indicated that GR and LEDGF/p75 belong to the same transcriptional network, and immunochemical studies demonstrated their co-immunoprecipitation and co-localization in DTX-resistant cells. The GR modulators exicorilant and relacorilant increased the sensitivity of chemoresistant PCa cells to DTX-induced cell death, and this effect was more pronounced upon LEDGF/p75 silencing. RNA-sequencing of DTX-resistant cells with GR or LEDGF/p75 knockdown revealed a transcriptomic overlap targeting signaling pathways associated with cell survival and proliferation, cancer, and therapy resistance. These studies implicate the GR–LEDGF/p75 axis in PCa therapy resistance and provide a pre-clinical rationale for developing novel therapeutic strategies for advanced PCa.

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