Dual‐specificity phosphatase 6 plays a critical role in the maintenance of a cancer stem‐like cell phenotype in human endometrial cancer

Abstract

The prognosis of patients with high‐grade or advanced‐stage endometrial cancer remains poor. As cancer stem‐like cells (CSCs) are thought to be associated with endometrial cancers, it is essential to investigate the molecular mechanisms that regulate endometrial CSCs. Dual‐specificity phosphatase 6 (DUSP6) functions as a negative‐feedback regulator of MAPK–ERK1/2 signaling, but its role in endometrial cancer remains unknown. We investigated whether DUSP6 is involved in cancer cell stemness using endometrial cancer cell lines and specimens from endometrial cancer patients. DUSP6 induced the expression of CSC‐related genes including ALDH1, Nanog, SOX2 and Oct4A, increased the population of cells in the G0/G1 phase, and promoted sphere formation ability. DUSP6 knockdown resulted in reduced cell invasion and metastasis, whereas DUSP6 overexpression inhibited apoptosis under serum‐free conditions. Moreover, DUSP6 decreased phosphorylated ERK1/2 and increased phosphorylated Akt levels, which potentially induces CSC features. In patients with endometrial cancers, DUSP6 expression was determined using immunohistochemistry, and based on the results, the patients were dichotomized into high‐ and low‐DUSP6‐expression groups. Progression‐free survival and overall survival were significantly shorter in the high‐DUSP6‐expression group. These results suggest that DUSP6 has potential value as a biomarker of CSCs and as a target of therapies designed to eliminate CSCs in endometrial cancer.

Downregulation of 5-hydroxymethylcytosine is associated with the progression of cervical intraepithelial neoplasia

“…For A3B, endogenous peroxidases were blocked using 3% hydrogen peroxide in methyl alcohol for 15 min. The slides were incubated with a primary antibody at 4°C overnight and with a secondary antibody at room temperature for 1 h. The IHC signal was detected using DAB (Wako), and the nuclei were stained with hematoxylin as we have described previously [ 14 ]. In each case, the total IHC score was calculated by at least 2 examiners using a BZ-X710 microscope (Keyence).…”

PHF20 inhibition promotes apoptosis and cisplatin chemosensitivity via the OCT4‑p‑STAT3‑MCL1 signaling pathway in hypopharyngeal squamous cell carcinoma

“…Among OCT4 isoforms, OCT4B1 and OCT4A serve important roles in apoptosis ( 25 , 31 , 33 ). Therefore, we hypothesized that OCT4B1 and OCT4A rather than other OCT4 isoforms may mediate the apoptosis induced by PHF20 knockdown.…”

“…A previous study has demonstrated that PHF20 is involved in tumorigenesis ( 25 ). However, the expression level and role of PHF20 in apoptosis and cisplatin sensitivity remain unclear.…”

DUSP7 inhibits cervical cancer progression by inactivating the RAS pathway

“…DUSP4 is considered a candidate tumour suppressor gene, and its deletion is related to the occurrence of breast cancer, rectal cancer, thyroid cancer and other tumours 17,18 . DUSP6 is expressed at low levels in the tumour tissues of many human malignancies, including ovarian cancer and endometrial cancer 19,20 .…”