Cervical cancer stem cell‑associated genes: Prognostic implications in cervical cancer (Review)

Abstract

Cervical cancer is the fourth most common type of gynecological malignancy to affect females, worldwide. Although high-risk human papillomavirus (HR-HPV) infection is the primary etiologic agent associated with the development of cervical cancer, cancer stem cells (CSCs) also serve a prominent role in the development, metastasis, recurrence and prognosis of the disease. CSCs are a small subpopulation of cells that have the ability to self-renew and are present in the majority of tumors, including cervical cancer. Studies describing the phenotype of cervical CSCs (CCSCs) vary in their definition of the expression pattern of principal biomarkers, including Musashi-1, aldehyde dehydrogenase 1, Oct3/4, Sox2 and CD49f. However, these markers are not observed in all cancers, although several may be present in multiple tumor types. The present review describes the potential biomarkers of CSCs in cervical cancer. These CCSC biomarkers may serve as molecular targets to enhance the efficacy and reduce the side effects associated with chemotherapeutic treatment in HR-HPV-positive cervical cancer.

A possible interplay between HR‐HPV and stemness in tumor development: an in vivo investigation of CD133 as a putative marker of cancer stem cell in HPV18‐infected KB cell line

“…These cells, able to forming a tumor, named tumor-initiating cells (TICs), have been supposed to originate from the stem cell compartments, and many researchers verified this hypothesis in different types of tumors. Several cell surface markers and transcription factors such as CD44, CD133, CK17, aldehyde dehydrogenase 1 (ALDH1), Nanog, and Oct4 have been utilized to isolate and enrich CSC populations from different tumors (17)(18)(19)(20).…”

“…The first studies documenting the CSC theory were carried out on acute myelogenous leukemia (6,7). Subsequently, numerous evidences on other solid tumors such as breast, brain, colon, prostate, lung cancers, and melanoma suggested that a minority of malignant stem cells, able to selfrenewal, sustains tumor growth and is responsible of therapeutic failure and clinically adverse outcome (3,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20).…”

“…Several cell surface markers and transcription factors such as CD133, CD44, CK17, aldehyde dehydrogenase 1 (ALDH1), Nanog, and Oct4 have been utilized to isolate and enrich CSC populations from different tumors (17)(18)(19)(20). High expression levels of these CSC markers have been related to increased self-renewal properties, proliferation, and resistance to radiotherapy.…”

<p>Enhanced and Prolonged Antitumor Effect of Salinomycin-Loaded Gelatinase-Responsive Nanoparticles via Targeted Drug Delivery and Inhibition of Cervical Cancer Stem Cells</p>

“…We next examined the expression of the cervical CSC-related markers CD44 and CD133. 42,43 The IHC and WB analyses showed that mice receiving Sal exhibited markedly lower levels of CD133 and CD44 than their control counterparts ( Figure 4A and C). Among all the groups, the Sal NP 2-treated group showed the strongest inhibition of CSCs.…”

Role of Oct3/4 in Cervical Cancer Tumorigenesis

“…During HR-HPV infection, the virus binds to the receptors on the target cell surface, resulting in its internalization, and subsequently, the viral DNA is released and transported to the cell nucleus (45,64). After the viral DNA is integrated, it synthesizes the E6 and E7 oncoproteins that promote proliferation for TP53 degradation by E6 and pRB degradation by E7; it has been observed that the degradation of pRb leads to the overexpression of OCT3/4 and that the degradation of p53 leads to an increase in the expression of NANOG (65,66), and it is well known that NANOG can directly bind to the OCT3/4 gene promoter to induce its expression (67-69).…”