Role of the Sterol Regulatory Element Binding Protein Pathway in Tumorigenesis

Abstract

Metabolic changes are a major feature of tumors, including various metabolic forms, such as energy, lipid, and amino acid metabolism. Sterol regulatory element binding proteins (SREBPs) are important modules in regulating lipid metabolism and play an essential role in metabolic diseases. In the previous decades, the regulatory range of SREBPs has been markedly expanded. It was found that SREBPs also played a critical role in tumor development. SREBPs are involved in energy supply, lipid supply, immune environment and inflammatory environment shaping in tumor cells, and as a protective umbrella to support the malignant proliferation of tumor cells. Natural medicine and traditional Chinese medicine, as an important part of drug therapy, demonstrates the multifaceted effects of SREBPs regulation. This review summarizes the core processes in the involvement of SREBPs in tumors and provides a comprehensive understanding of the pathways through which natural drugs target the SREBP pathway and regulate tumor progression.

SREBP1 activation contributes to fatty acid accumulations in necroptosis

“…Activation of de novo lipogenesis due to SREBP activation is related to several pathologies, including the progression of different forms of cancers. 53, 54 In these systems, increased de novo lipid biosynthesis provides the necessary building blocks for uncontrolled cell division. 53 Other than potential implications in cancer therapeutics, blocking SREBP activation and decreasing lipid content in vivo has shown promising potential to combat metabolic diseases such as type II diabetes and atherosclerosis.…”

“…53, 54 In these systems, increased de novo lipid biosynthesis provides the necessary building blocks for uncontrolled cell division. 53 Other than potential implications in cancer therapeutics, blocking SREBP activation and decreasing lipid content in vivo has shown promising potential to combat metabolic diseases such as type II diabetes and atherosclerosis. 55 Our results reveal a new role of SREBP1 activation, shed light on important mechanisms of lipid regulations during necroptosis, and provide potential targets for diseases that involve this process.…”

6-Shogaol Antagonizes the Adipocyte-Conditioned Medium-Initiated 5-Fluorouracil Resistance in Human Colorectal Cancer Cells through Controlling the SREBP-1 Level

“…SREBP-1 is a nuclear protein that could act as a transcription factor involved in cholesterol metabolism and the modulation of lipid synthesis-related gene transcription. However, increasing evidence has also supported the concept that SREBP-1 could play an important role in tumor progression and malignancy [ 19 , 20 , 21 , 22 ]. Moreover, a positive correlation between CRC development and SREBP-1 upregulation has been further found in clinical findings [ 22 , 23 ].…”

“…Lipid is one of the energy resources for normal cell survival and is also a major ingredient of cell membranes. Therefore, an explanation of the clinical positive correlation between SREBP-1 upregulation and cancer development is that SREBP-1 increases the lipid synthesis in order to flatter the abnormal energy demand and cell division of cancer cells [ 19 ]. On the other hand, SREBP-1 has also been reported to affect the apoptosis of cancer cells by inhibiting the expression of the apoptotic factor [ 24 ].…”

Concomitant Inhibition of FASN and SREBP Provides a Promising Therapy for CTCL

“…However, metabolic reprograming has become a hallmark of cancer cells, which, unlike normal cells that can acquire sufficient lipids from dietary intake and hepatic DNL, they need extra lipids to sustain tumour survival and growth [ 7 ]. In this case, a variety of tumours overexpress FASN, including liver, pancreas, gastric, colorectal, ovarian, breast, and prostate cancer, which is often associated with poor prognosis [ 8 , 9 , 10 , 11 , 12 , 13 , 14 ].…”