Open AccessCross-talk between mutant p53 and p62/SQSTM1 augments cancer cell migration by promoting the degradation of cell adhesion proteins
Author(s) -
Saptaparna Mukherjee,
Martino Maddalena,
YiQing Lü,
Sébastien Martinez,
Nishanth Belugali Nataraj,
Ashish Noronha,
Sansrity Sinha,
Katie Teng,
Victoria CohenKaplan,
Tamar Ziv,
Sharathchandra Arandkar,
Ori Hassin,
Rishita Chatterjee,
Anna-Chiara Pirona,
Michal Shreberk-Shaked,
Anat Gershoni,
Yael Aylon,
Zvulun Elazar,
Daniel Schramek,
Moshe Oren
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2119644119
Subject(s) - microbiology and biotechnology , cell migration , biology , mutant , cell , cancer cell , cell growth , cancer research , cancer , genetics , gene
Significance Missense mutations in theTP53 gene, encoding the p53 tumor suppressor, are very frequent in human cancer. Some of those mutations, particularly the more common (“hotspot”) ones, not only abrogate p53’s tumor suppressor activities but also endow the mutant protein with oncogenic gain of function (GOF). We report that p53R273H , the most common p53 mutant in pancreatic cancer, interacts with the SQSTM1/p62 protein to accelerate the degradation of cell adhesion proteins. This enables pancreatic cancer cells to detach from the epithelial sheet and engage in individualized cell migration, probably augmenting metastatic spread. By providing insights into mechanisms that underpin mutant p53 GOF, this study may suggest ways to interfere with the progression of cancers bearing particular p53 mutants.