Tabriz University of Medical Sciences Advanced Pharmaceutical Bulletin 2228-5881 16 3 2026 09 30 Interplay Between Endolysosomal Calcium Signalling, EMT, and Autophagy in Colorectal Cancer (CRC): Implications for Metastasis and Therapeutic Strategies 482 494 10.34172/apb.45688 EN Nur Aqilah Nadhirah Affendie https://orcid.org/0009-0001-9082-2731 Nurul Syahmin Ab Aziz Siti Yusrina Nadihah Jamaludin Normala Abd Latip Aisyah Hasyila Jahidin https://orcid.org/0000-0002-4968-2685 REVIEW 10.34172/apb.45688 2025 05 05 2026 06 21 Colorectal cancer (CRC) is a form of cancer that, while initially slow to develop, becomes aggressive and poses significant treatment challenges in its later stages, often resulting in a low survival rate. This progression is evident, with patients having an approximate 90% five-year survival rate at the localised stage CRC, which drops dramatically to 12.5% for those with distant metastases. Epithelial-to-mesenchymal transition (EMT) plays a pivotal role in metastases, as it facilitates the spread of cancer cells to migrate from the primary site to secondary locations. Autophagy further supports this process by enhancing cell survival under stress. Both EMT and autophagy are tightly regulated by calcium signalling, which is essential for cancer cell migration, invasion, and survival under unfavourable conditions. Targeting specific calcium channels and signalling pathways can inhibit EMT and regulate autophagy, thereby reducing cancer metastasis. This review explores the intricate relationship between endolysosomal (EL) calcium signalling, EMT, and autophagy in CRC, highlighting potential therapeutic strategies and the significance of these findings for improving treatment outcomes.