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Dissecting the multifaceted roles of autophagy in cancer initiation, growth, and metastasis: from molecular mechanisms to therapeutic applications

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Abstract

Autophagy is a cytoplasmic defense mechanism that cells use to break and reprocess their intracellular components. This utilization of autophagy is regarded as a savior in nutrient-deficient and other stressful conditions. Hence, autophagy keeps contact with and responds to miscellaneous cellular tensions and diverse pathways of signal transductions, such as growth signaling and cellular death. Importantly, autophagy is regarded as an effective tumor suppressor because regular autophagic breakdown is essential for cellular maintenance and minimizing cellular damage. However, paradoxically, autophagy has also been observed to promote the events of malignancies. This review discussed the dual role of autophagy in cancer, emphasizing its influence on tumor survival and progression. Possessing such a dual contribution to the malignant establishment, the prevention of autophagy can potentially advocate for the advancement of malignant transformation. In contrast, for the context of the instituted tumor, the agents of preventing autophagy potently inhibit the advancement of the tumor. Key regulators, including calpain 1, mTORC1, and AMPK, modulate autophagy in response to nutritional conditions and stress. Oncogenic mutations like RAS and B-RAF underscore autophagy's pivotal role in cancer development. The review also delves into autophagy's context-dependent roles in tumorigenesis, metastasis, and the tumor microenvironment (TME). It also discusses the therapeutic effectiveness of autophagy for several cancers. The recent implication of autophagy in the control of both innate and antibody-mediated immune systems made it a center of attention to evaluating its role concerning tumor antigens and treatments of cancer.

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Data availability

The dataset used in this study will be available as per request (mailing to the corresponding author).

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A.A., M.K.H., Z.M. and Y.K. conceptualized the manuscript; A.A., M.K.H., Z.M., M.S.H. and Y.K. wrote the manuscript; M.K.H., Z.M. and Y.K. critically reviewed and edited the manuscript. All authors approved the submitted version of the manuscript.

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Ayub, A., Hasan, M.K., Mahmud, Z. et al. Dissecting the multifaceted roles of autophagy in cancer initiation, growth, and metastasis: from molecular mechanisms to therapeutic applications. Med Oncol 41, 183 (2024). https://doi.org/10.1007/s12032-024-02417-2

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