Autophagy Involvement in Non-Neoplastic and Neoplastic Endometrial Pathology: The State of the Art with a Focus on Carcinoma

Abstract

Autophagy is a cellular process crucial for maintaining homeostasis by degrading damaged proteins and organelles. It is stimulated in response to stress, recycling nutrients and generating energy for cell survival. In normal endometrium, it suppresses tumorigenesis by preventing toxic accumulation and maintaining cellular homeostasis. It is involved in the cyclic remodelling of the endometrium during the menstrual cycle and contributes to decidualisation for successful pregnancy. Such a process is regulated by various signalling pathways, including PI3K/AKT/mTOR, AMPK/mTOR, and p53. Dysregulation of autophagy has been associated with benign conditions like endometriosis and endometrial hyperplasia but also with malignant neoplasms such as endometrial carcinoma. In fact, it has emerged as a crucial player in endometrial carcinoma biology, exhibiting a dual role in both tumour suppression and tumour promotion, providing nutrients during metabolic stress and allowing cancer cell survival. It also regulates cancer stem cells, metastasis and therapy resistance. Targeting autophagy is therefore a promising therapeutic strategy in endometrial carcinoma and potential for overcoming resistance to standard treatments. The aim of this review is to delve into the intricate details of autophagy's role in endometrial pathology, exploring its mechanisms, signalling pathways and potential therapeutic implications.

Keywords: autophagy; endometrial carcinoma; endometriosis; targeted therapies.

Figure 1

Mechanisms of autophagy flux in normal, hyperplastic and dysfunctional uterine pathology (the figure was created with BioRender.com, accessed on 21 August 2024).

Figure 2

The main autophagic-related proteins involved in endometrial carcinoma.