Autophagy regulates apoptosis of colorectal cancer cells based on signaling pathways

Abstract

Colorectal cancer is a common malignant tumor of the digestive system. Its morbidity and mortality rank among the highest in the world. Cancer development is associated with aberrant signaling pathways. Autophagy is a process of cell self-digestion that maintains the intracellular environment and has a bidirectional regulatory role in cancer. Apoptosis is one of the important death programs in cancer cells and is able to inhibit cancer development. Studies have shown that a variety of substances can regulate autophagy and apoptosis in colorectal cancer cells through signaling pathways, and participate in the regulation of autophagy on apoptosis. In this paper, we focus on the relevant research on autophagy in colorectal cancer cells based on the involvement of related signaling pathways in the regulation of apoptosis in order to provide new research ideas and therapeutic directions for the treatment of colorectal cancer.

Keywords: Apoptosis; Autophagy; Colorectal cancer; Signaling pathways.

Fig. 1

Mechanism of action of three types of autophagy. A Macroautophagy: ➀ membrane initiation and extension. ➁ Formation of autophagosomes. ➂ autophagosomes fuse with lysosomes to form autolysosomes. B Microautophagy: a Lysosomal protruding microautophagy. b Lysosomal invagination type microautophagy. C CMA

Fig. 2

A Bidirectional regulatory role of autophagy in colorectal cancer: a promoting, b inhibiting. B Multiple compounds regulate apoptosis in CRC cells via autophagy

Fig. 3

PI3K/AKT/mTOR signaling pathway. Membrane receptors PTK bind GF (growth factor) and phosphorylate to form dimers. Phosphorylated PTK dimers bind IRS, IRS binds PI3K, and PI3K is activated. Phosphorylation of PIP2 to PIP3 and PIP2 to PIP3 by PI3K is reversible and PTEN is involved in the dephosphorylation of PIP3. PAKT is phosphorylated by IP3 activation. The PI3K/AKT/mTOR signaling pathway includes both positive and negative feedback. In negative feedback, downstream of AKT is the mTOR, AKT activates mTORC1, mTORC1 activates S6K, and then phosphorylates IRS. TRS phosphorylation is followed by inhibitory activity and is unable to activate PI3K, decreasing the AKT activation. In positive feedback regulation, activation of AKT activates IKK, which then activates the NF‐κB signaling pathway, inhibits PTEN expression, attenuates PIP3 dephosphorylation, accumulates PIP3, and increases AKT activation. mTORC1 downstream genes also include ULK1, which inhibits autophagy following mTORC1 phosphorylation, and ULK1