Being the 5th most common cancer, Gastric cancer (GC) accounts for > 8.2% of all cancer mortality worldwide [1–4]. At this rate, by 2050, there will be approximately 2,500,000 new cases and 1,900,000 fatalities [5]. The rate of GC incidence is known to increase with age and is more prevalent in men [6, 7]. Helicobacter pylori, one of the pathogens that induces chronic gastritis, is known to account for > 60% of cases of GCs [8–10]. Other factors, such as diet, lifestyle, genetic factors, socioeconomic factors, etc., also contribute to GC occurrence [6, 7]. The Lauren classification describes two types of gastric cancer based on histology: intestinal and diffuse [6]. GC has a poor prognosis, with a worldwide five-year rate of survival between 10% and 40% and 20% for developing countries [5].
Autophagy is an intracellular degradation process that occurs to maintain cellular homeostasis under stress, such as lack of nutrients, loss of energy, and oxygen deficiency [11]. Mammalian cells represent three primary types of autophagy: micro-, macro-, and chaperone-mediated autophagy involving initiation, nucleation, maturation, and degradation [12, 13]. This lysosome-dependent process is critically involved in cellular processes related to immunity/inflammation, metabolism, and survival, and thus, any dysfunction is known to result in major dysfunctioning of the major organ systems, such as the heart, lung, liver, brain, etc. [12, 14, 15]. Additionally, apoptosis-resistant tumor cells can be killed via autophagy, which, in turn, can be activated by multiple signaling pathways [16]. Also, previous studies have reported that autophagy elicits both tumor and anti-tumor responses [17].
One of the critical components of the human body’s innate immune response is Toll-like receptors (TLRs) [18–20]. They are known to regulate tissue damage and tumor progression processes [19]. They identify pathogen-associated molecular patterns (PAMPs), which are conserved microbial structures, such as peptidoglycan, lipopolysaccharide, synthetic double-stranded RNA, CpG DNA motifs associated with bacterial DNA, and flagellin, which bind to TLR2, TLR4, TLR3, TLR9, TLR5, respectively [18, 21]. Per previous studies, 10 functional human TLRs and 12 functional mice TLRs have been identified, with TLR1-9 being conserved in both species, whereas TLR10 in humans alone [20, 22, 23]. TLR4 has been found in various cell types, such as immune cells and cardiomyocytes [11]. TLRs are also involved in cancer pathogenesis [22, 24, 25]. As the most classical TLR in helicobacter pylori-mediated GC, TLR4 plays a critical role in immunotherapy of GC [26–28]. TLR4 is also expressed in various other cancers [29, 30]. However, the physiological role of TLR4 in GC autophagy and its underlying mechanism needs further exploration.
Here, we first analyzed the levels in GC cells/tissues, including SGC-7901/ GES-1/ MGC-803/ and BGC-823/. Furthermore, we analyzed the role and underlying mechanism of TLR4 in autophagy and cellular growth in GC. The data presented in this analysis suggested that TLR4 was crucially involved in GC pathophysiology and could act as a diagnostic and medical target in GC.