AP 18 synthesis On the contrary evidence also suggests that

On the contrary, evidence also suggests that autophagy plays a striking protective role in cancer cells. Highly burgeoning cancer AP 18 synthesis require cellular building blocks for their metabolism and energy production. At this stage of cancer development, autophagy acts as a friend providing all the essential cellular intermediates to satisfy the metabolic demands of proliferating tumorigenic cells. To validate the protective role of autophagy in cancer cells, it has been demonstrated that tongue squamous cell carcinoma (TSCC) shows cisplatin resistance via autophagy activation. The treatment of TSCC with chloroquine (CQ) and Beclin1 siRNA increased cisplatin sensitivity, strengthening the fact that autophagy inhibition can be a potential target for treating TSCC [25]. Nonetheless, the resistance property of the oral squamous cell carcinoma (OSCC) against cisplatin has also been shown to be regulated by increased autophagic flux. The Fadu-CDDP-R (Fadu cisplatin resistant) cells showed increased autophagic markers, such as Beclin1, Ulk1, Atg5, Atg7, and Atg14. In the same context, the surface resistant marker, CD44 was found to be decreased in Atg14-deficient Fadu cells [26]. Other reports show that the over-expression of phospholipase C (PLC) reduced autophagy in response to anti-cancer drug oxaliplatin and induced cell death. These observations emphasize the negative effect of PLC on autophagy and attest that autophagy promotes tumorigenesis. Additionally, miRNA has been found to induce autophagy in colorectal cancer, thereby enhancing cancer progression as well as chemotherapeutic resistance. miR-18a and miR-124 induces autophagy, promoting cancer progression whereas miR-210 provides chemoresistance by inducing autophagy [27]. As another example, in prostate cancer (PC3) cell lines, celecoxib has been found to induce apoptosis. Additionally, it exerts its protective role against prostate cancer cells by stimulating JNK-mediated autophagy. Therefore, the obstruction of the JNK-mediated autophagy can be a strategy to inhibit prostate cancer [28]. Autophagy has been shown to play a prominent role in cancer progression by favoring cellular metabolites and redox homeostasis. During hypoxic conditions, cancer cells consume glucose through anaerobic glycolysis, known as Warburg effect to provide unlimited pool of glycolytic intermediates. For example, glycolytic enzyme pyruvate kinase M1 (PKM1)-activated autophagy contributes to tumor malignancy in KrasG12D mouse model. Moreover, PKM1-Atg7 knockout mice showed decreased tumor growth as compared to wild type ATG7 cells. [29]. In addition, cancer cells exhibit higher glutamine utilization leading to autophagy induction through mTOR inactivation for survival of the cancer cells in harsh microenvironmental conditions. [30]. Autophagy in endothelial, stromal and immune cells present in tumor microenvironment has been documented to play prominent role in modulation of cancer growth and progression. The features of the tumor microenvironment including deprived nutrient condition, limited energy, hypoxia are responsible for inducing autophagy through different pathways leading tumor development to metastasis. It showed that autophagy in innate immune cell including NK cells, macrophages and neutrophil play a dual role in regulating tumor growth and progression in context dependent manner [31]. Moreover, autophagy in dendritic cells (DCs) facilitates the efficient processing and presentation of the intracellular antigens on MHC class I or II [32]. In addition, autophagy promotes the liberation of ATP and damage-associated molecular patterns (DAMPs) from dying tumor cells and therefore presenting it to the CD8+ cytotoxic lymphocytes that results in the clearance of the tumor cells [33]. Cancer associated adipocytes (CAAs) and cancer associated fibroblasts (CAFs) has found to exhibit increase in autophagic flux in response to hypoxia and ROS production by malignant cells as compared to normal counterparts [32]. On the other hand, it was demonstrated that lncRNA CPS-IT suppressed metastasis and epithelial-mesenchymal transition by inhibiting hypoxia-induced autophagy in colorectal carcinoma suggesting the fact that inhibition of autophagy inhibits metastasis [34].