RRC ID 72307
Author Singh G, Chakraborty S, Lakhotia SC.
Title Elevation of major constitutive heat shock proteins is heat shock factor independent and essential for establishment and growth of Lgl loss and Yorkie gain-mediated tumors in Drosophila.
Journal Cell Stress Chaperones
Abstract Cancer cells generally overexpress heat shock proteins (Hsps), the major components of cellular stress response, to overcome and survive the diverse stresses. However, the specific roles of Hsps in initiation and establishment of cancers remain unclear. Using loss of Lgl-mediated epithelial tumorigenesis in Drosophila, we induced tumorigenic somatic clones of different genetic backgrounds to examine the temporal and spatial expression and roles of major heat shock proteins in tumor growth. The constitutively expressed Hsp83, Hsc70 (heat shock cognate), Hsp60 and Hsp27 show elevated levels in all cells of the tumorigenic clone since early stages, which persists till their transformation. However, the stress-inducible Hsp70 is expressd only in a few cells at later stage of established tumorous clones that show high F-actin aggregation. Intriguingly, levels of heat shock factor (HSF), the master regulator of Hsps, remain unaltered in these tumorous cells and its down-regulation does not affect tumorigenic growth of lgl- clones overexpressing Yorkie, although down-regulation of Hsp83 prevents their survival and growth. Interestingly, overexpression of HSF or Hsp83 in lgl- cells makes them competitively successful in establishing tumorous clones. These results show that the major constitutively expressed Hsps, but not the stress-inducible Hsp70, are involved in early as well as late stages of epithelial tumors and their elevated expression in lgl- clones co-overexpressing Yorkie is independent of HSF.
Volume 27(4)
Pages 431-448
Published 2022-7-1
DOI 10.1007/s12192-022-01283-z
PII 10.1007/s12192-022-01283-z
PMID 35704239
PMC PMC9346025
MeSH Animals Drosophila* HSP27 Heat-Shock Proteins HSP70 Heat-Shock Proteins / genetics HSP70 Heat-Shock Proteins / metabolism Heat-Shock Proteins / genetics Heat-Shock Response / genetics Neoplasms* / genetics
IF 2.892
Drosophila 1242R-1