Cancer is a devastating disease that progresses when cells divide uncontrollably and spread to other parts of the body, but scientists have found that neighboring noncancerous cells are often able to inhibit the growth of tumor cells in a process known as contact normalization. Tumor cells must somehow overcome this inhibition to become malignant, but exactly how they do this has not yet been resolved. To fill this gap, researchers recently used microscopy, CRISPR, and RNA sequencing techniques to uncover how noncancerous cells influence adjacent cancerous cells. They found that contact normalization takes place when noncancerous cells use the protein N-cadhedrin to adhere to neighboring tumor cells. This results in a decrease in the expression of the protein podoplanin and the inhibition of tumor cell proliferation. The team also concluded that the presence of podoplanin enables cancerous cells to override contact normalization under continued N-cadherin expression. While the related signaling mechanisms have yet to be completely defined, these findings suggest that podoplanin could be a promising chemotherapy target and lend cellular level insights that could inform the development of new cancer treatments.