To Divide or Invade: A Look Behind the Scenes of the Proliferation-Invasion Interplay in the Caenorhabditis elegans Anchor Cell

Abstract

Cell invasion is defined by the capability of cells to migrate across compartment boundaries established by basement membranes (BMs). The development of complex organs involves regulated cell growth and regrouping of different cell types, which are enabled by controlled cell proliferation and cell invasion. Moreover, when a malignant tumor takes control over the body, cancer cells evolve to become invasive, allowing them to spread to distant sites and form metastases. At the core of the switch between proliferation and invasion are changes in cellular morphology driven by remodeling of the cytoskeleton. Proliferative cells utilize their actomyosin network to assemble a contractile ring during cytokinesis, while invasive cells form actin-rich protrusions, called invadopodia that allow them to breach the BMs. Studies of developmental cell invasion as well as of malignant tumors revealed that cell invasion and proliferation are two mutually exclusive states. In particular, anchor cell (AC) invasion during Caenorhabditis elegans larval development is an excellent model to study the transition from cell proliferation to cell invasion under physiological conditions. This mini-review discusses recent insights from the C. elegans AC invasion model into how G1 cell-cycle arrest is coordinated with the activation of the signaling networks required for BM breaching. Many regulators of the proliferation-invasion network are conserved between C. elegans and mammals. Therefore, the worm may provide important clues to better understand cell invasion and metastasis formation in humans.

Trade-offs between chemotaxis and proliferation shape the phenotypic structuring of invading waves

“…The assumptions ( 4) and ( 6) on ∂ ρ R correspond to saturating growth, while the assumptions ( 4) and ( 6) on ∂ y R model the fact that cells with a higher chemotactic sensitivity are characterised by a lower proliferation rate, for example due to the energetic cost of sensing chemotactic cues [17] or the acquisition of pro-invasion gene expression and cell signatures being contingent on cell cycle arrest [18]. Furthermore, the assumption (6) on ∂ S R translates in mathematical terms to the idea that, when the attractant is considered to be of nutrient-like form, higher levels of attractant availability may correlate with faster cell proliferation.…”

“…the proliferation rate of cells in the phenotypic state y = 0), and γ > 0 describes the rate at which a cell degrades the attractant. Note that when r(y) is defined via (18), the local carrying capacity of the cell population is ρ M = β.…”

“…the function κ(y, S ε ) satisfies assumptions (10)). In the former we again define the function κ via (18), while in the latter case we let attractant degradation be proportional to the cell proliferation rate (i.e. κ(y, S ε ) ∝ r(y, S ε )) and thus use the following definition…”

“…Hence, we suppose the fitness function R(y, ρ ε , S ε ) satisfies assumptions ( 5)-( 7), again taking the form (21) with r(y, S ε ) defined via (22). Furthermore, we again consider the linear chemotactic sensitivity function χ(y) defined via (18), and consider the case where degradation of the attractant is proportional to the cell proliferation rate, i.e. κ(y, S) is given by (23).…”

YBX1 integration of oncogenic PI3K/mTOR signalling regulates the fitness of malignant epithelial cells

“…While proliferative and invasive cancer cells retain common genetic alterations, discrete molecular processes evolve in proliferating cancer cells to acquire an invasive potential [11][12][13] . However, molecular factors responsible for the proliferative to invasive switch remain poorly understood and represent an attractive, yet unexplored therapeutic opportunity against metastatic cancers.…”