Title:The Role of Hypoxia in Endometrial Cancer
Volume: 23
Issue: 2
Author(s): Yarely M. Salinas-Vera, Dolores Gallardo-Rincón, Erika Ruíz-García, Macrina B. Silva-Cázares, Carmen Sol de la Peña-Cruz and César López-Camarillo*
Affiliation:
- Posgrado en Ciencias Genómicas, Universidad
Autónoma de la Ciudad de México, Ciudad de México, México
Keywords:
Endometrial cancer, hypoxia, HIF-1α, microRNAs, therapy, chemotherapy.
Abstract: Endometrial cancer represents the most frequent neoplasia from the corpus uteri and comprises
the 14th leading cause of death in women worldwide. Risk factors that contribute to the disease
include early menarche, late menopause, nulliparity, and menopausal hormone use, as well as hypertension
and obesity comorbidities. The clinical effectiveness of chemotherapy is variable, suggesting
that novel molecular targeted therapies against specific cellular processes associated with the maintenance
of cancer cell survival and therapy resistance ameliorate the rates of success in endometrial
cancer treatment. In the course of tumor growth, cancer cells must adapt to decreased oxygen availability
in the microenvironment by upregulation of hypoxia-inducible factors, which orchestrate the
activation of a transcriptional program leading to cell survival. During this adaptative process, the
hypoxic cancer cells may acquire invasive and metastatic properties as well as increased cell proliferation
and resistance to chemotherapy, enhanced angiogenesis, vasculogenic mimicry, and maintenance
of cancer cell stemness, which contribute to more aggressive cancer phenotypes. Several studies
have shown that hypoxia-inducible factor 1 alpha (HIF-1α) protein is aberrantly overexpressed in
many solid tumors of the breast, prostate, ovarian, bladder, colon, brain, and pancreas. Thus, it has
been considered an important therapeutic target. Here, we reviewed the current knowledge of the
relevant roles of cellular hypoxia mechanisms and HIF-1α functions in diverse processes associated
with endometrial cancer progression. In addition, we also summarize the role of microRNAs in the
posttranscriptional regulation of protein-encoding genes involved in the hypoxia response in endometrial
cancer. Finally, we pointed out the need for urgent targeted therapies to impair the cellular
processes activated by hypoxia in the tumor microenvironment.