Targeting Autophagy in Thyroid Cancer: EMT, Apoptosis, and Cancer Stem Cells

Abstract

Autophagy is a highly conserved recycling process through which cellular homeostasis is achieved and maintained. With respect to cancer biology, autophagy acts as a double-edged sword supporting tumor cells during times of metabolic and therapeutic stress, while also inhibiting tumor development by promoting genomic stability. Accumulating evidence suggests that autophagy plays a role in thyroid cancer, acting to promote tumor cell viability and metastatic disease through maintenance of cancer stem cells (CSCs), supporting epithelial-to-mesenchymal transition (EMT), and preventing tumor cell death. Intriguingly, well-differentiated thyroid cancer is more prevalent in women as compared to men, though the underlying molecular biology driving this disparity has not yet been elucidated. Several studies have demonstrated that autophagy inhibitors may augment the anti-cancer effects of known thyroid cancer therapies. Autophagy modulation has become an attractive target for improving outcomes in thyroid cancer. This review aims to provide a comprehensive picture of the current knowledge regarding the role of autophagy in thyroid cancer, focusing on the potential mechanism(s) through which inhibition of autophagy may enhance cancer therapy and outcomes.

Transcription factor FOXP4 inversely governs tumor suppressor genes and contributes to thyroid cancer progression

“…Analysis of metastatic pleural effusion in KTC-1 cells [ 24 ] revealed their enhanced migratory potential compared to cancer cells isolated from the primary lesion. The EMT process weakens and disrupts connections between epithelial cells, enhancing tumor cell motility and migration, ultimately increasing tumor cell invasiveness and the likelihood of distant metastasis [ 25 , 26 ].…”

Construction and validation of a PANoptosis-related lncRNA signature for predicting prognosis and targeted drug response in thyroid cancer

“…In 2020, Karki et al (2020) found that activation of IRF1-dependent “PANoptosis” in a mouse model of colorectal cancer could prevent AOM/DSS-induced colorectal carcinogenesis. In addition, accumulating evidence suggests that a broad range of programmed cell death processes, including apoptosis, pyroptosis, and necroptosis, play an important role in TC ( Holm et al, 2022 ). Most of the research on PANoptosis has focused on molecular mechanisms.…”

NRP1 regulates autophagy and proliferation of gastric cancer through Wnt/β-catenin signaling pathway

“…Although most previous studies have reported that cellular autophagy is a self-protective mechanism to prevent cancer development, cellular autophagy can also perform proto-oncogenic functions to promote cancer development. For example, cancer metastasis occurs in a number of steps, including angiogenesis, alteration of the tumour microenvironment, changes in the extracellular matrix and the Epithelial-mesenchymal transition (EMT) [ 22 , 23 ]. Cellular autophagy can both promote tumour metastasis in this process and stop it by degrading key proteins.…”