Proteomic and transcriptomic profiling identifies mediators of anchorage-independent growth and roles of inhibitor of differentiation proteins in invasive lobular carcinoma

Sci Rep. 2020 Jul 13;10(1):11487. doi: 10.1038/s41598-020-68141-9.


Invasive lobular carcinoma (ILC) is a histological subtype of breast cancer with distinct molecular and clinical features from the more common subtype invasive ductal carcinoma (IDC). ILC cells exhibit anchorage-independent growth in ultra-low attachment (ULA) suspension cultures, which is largely attributed to the loss of E-cadherin. In addition to anoikis resistance, herein we show that human ILC cell lines exhibit enhanced cell proliferation in ULA cultures as compared to IDC cells. Proteomic comparison of ILC and IDC cell lines identified induction of PI3K/Akt and p90-RSK pathways specifically in ULA culture in ILC cells. Further transcriptional profiling uncovered unique upregulation of the inhibitors of differentiation family transcription factors ID1 and ID3 in ILC ULA culture, the knockdown of which diminished the anchorage-independent growth of ILC cell lines through cell cycle arrest. We find that ID1 and ID3 expression is higher in human ILC tumors as compared to IDC, correlated with worse prognosis uniquely in patients with ILC and associated with upregulation of angiogenesis and matrisome-related genes. Altogether, our comprehensive study of anchorage independence in human ILC cell lines provides mechanistic insights and clinical implications for metastatic dissemination of ILC and implicates ID1 and ID3 as novel drivers and therapeutic targets for lobular breast cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Autoantigens / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cadherins / genetics
  • Carcinoma, Lobular / genetics*
  • Carcinoma, Lobular / pathology
  • Cell Differentiation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Inhibitor of Differentiation Protein 1 / genetics
  • Inhibitor of Differentiation Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / genetics
  • Membrane Proteins / genetics
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplasm Proteins / genetics
  • Phosphatidylinositol 3-Kinases / genetics
  • Proteomics*
  • Proto-Oncogene Proteins c-akt / genetics
  • Ribosomal Protein S6 Kinases, 90-kDa / genetics
  • Signal Transduction / genetics
  • Transcriptome / genetics*


  • Autoantigens
  • CIP2A protein, human
  • Cadherins
  • ID1 protein, human
  • Inhibitor of Differentiation Protein 1
  • Inhibitor of Differentiation Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Neoplasm Proteins
  • ID3 protein, human
  • Proto-Oncogene Proteins c-akt
  • RPS6KA1 protein, human
  • Ribosomal Protein S6 Kinases, 90-kDa