The Tumor Suppressive Roles and Prognostic Values of STEAP Family Members in Breast Cancer

Abstract

Objective. To investigate the expression patterns and prognostic values of STEAP family members in the occurrence and development of breast cancer. Materials and Methods. The Human Protein Atlas was used to analyze the expression level of STEAPs in human normal tissues and malignant tumors. ONCOMINE datasets were analyzed for the comparison of the STEAPs levels between malignant cancers and corresponding normal tissues. Kaplan-Meier plotter was used to analyze the prognostic value of STEAPs in breast cancer patients. Results. STEAPs were widely distributed in human normal tissues with diverse levels. Normally, it is predicted that STEAP1 and STEAP2 were involved in the mineral absorption process, while STEAP3 participated in the TP53 signaling pathway and iron apoptosis. The results from ONCOMINE showed downregulation of STEAP1, STEAP2, and STEAP4 in breast cancers. Survival analysis revealed that breast cancer patients with high levels of STEAP1, STEAP2, and STEAP4 had a good prognosis, while those with low expression had high overall mortality. Conclusion. STEAP1, STEAP2, and STEAP4 are predicted to be the potential prognostic biomarkers for breast cancer patients, providing novel therapeutic strategies for them.

Expression and Prognostic Analyses of the Significance of STEAP1and STEAP2 in Lung Cancer

“…STEAP2 has been reported to be downregulated in breast cancer [21]. STEAP2 overexpression signi cantly inhibited proliferation and clonogenesis in breast cancer cells.…”

“…Upregulation of STEAP2 can inhibit the invasion and metastasis of breast cancer cells by inhibiting epithelial-mesenchymal transformation by affecting transcription factors [14]. In contrast, STEAP2 is signi cantly overexpressed in prostate cancer, and its overexpression promotes the proliferation, migration, and invasion of tumor cells [21]. Activation of the ERK pathway by STEAP2 leads to partial stagnation of the g0-G1 cell cycle in cancer cells, increasing proliferation and tumor development [22].…”

“…Recent studies have reported that the STEAP family, as channel proteins or transporter proteins, may play a role in cell adhesion [3] and are widely expressed in normal human tissues. Its important role in normal pathological processes has previously been demonstrated through mineral absorption, TP53 regulation of cell death genes, and transcription of iron death [23]. STEAP1 is a complete membrane protein with sequence homology to three enzymes (STEAP2-STEAP4) that catalyzes NADPH-dependent iron (III) reduction [24].…”

The Usefulness of STEAP Proteins in Prostate Cancer Clinical Practice

“…STEAP family members are relatively new proteins and their potential as prognostic biomarkers have been demonstrated in breast cancer (56), glioblastoma (57,58), Ewing tumors (30), skin disorders (59) and prostate cancer (7). A recent study that explored the use of STEAP proteins as possible prognostic indicators in prostate cancer showed that only STEAP4 was overexpressed, and significantly associated with relapse (7).…”

Identification of a New Transcriptional Co-Regulator of STEAP1 in Ewing’s Sarcoma

“…It is a 339 amino acid transmembrane protein implicated in cell adhesion, regulation of reactive oxygen species levels, and acts as an ion channel or transporter for cell–cell communication [ 24 ]. STEAP1 expression is highly upregulated in several cancers, including prostate, bladder, pancreas, ovary, gastrointestinal tract, cervix, and testicular cancer, as well as ES [ 25 , 26 , 27 , 28 , 29 ]. In the case of ES, STEAP1 is a direct transcriptional target of EWSFLI1 [ 25 ].…”