The roles of integrins and tetraspanins in Apoptosis-induced proliferation

Yang, Lingling (2025). The roles of integrins and tetraspanins in Apoptosis-induced proliferation. University of Birmingham. Ph.D.

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Abstract

Apoptosis, the best-studied form of programmed cell death, is a critical process that eliminates damaged cells in response to environmental stress. It has been revealed that apoptotic cells can stimulate additional proliferation of their neighbouring healthy cells to maintain tissue homeostasis, a phenomenon termed apoptosis-induced proliferation (AiP). Uncontrolled AiP can lead to tissue overgrowth. Therefore, AiP is relevant to both regeneration and tumorigenesis. Caspases, key executioners of apoptosis, can trigger AiP via activation of the stress response c-Jun N-terminal kinase (JNK) signalling pathway and its downstream secretion of the mitogens such as Wingless (Wg/Wnt), Spitz (Spi/EGF) and Decapentaplegic (Dpp). Recent studies have also highlighted the importance of F-actin polymerisation in activating JNK, which further stimulates cell proliferation in response to apoptotic signals. However, our understanding of AiP is still far from complete. In my PhD project, genetic screens identified two groups of transmembrane proteins, integrins and tetraspanins, as critical regulators of AiP. Further epistasis analysis suggested that integrins modulate F-actin remodelling, which is essential for JNK activation and the subsequent AiP activation. Intriguingly, Drosophila orthologues of human tetraspanins CD63, CD81, CD82, and CD151 possess non-redundant roles during AiP, as inhibiting each one of them suppresses AiP. Moreover, they genetically interact with integrins in regulating actin dynamics, thereby mediating AiP. Therefore, my research has discovered and characterised the novel roles of integrins and tetraspanins in AiP, providing new insights into how they regulate this critical process.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):