The Hippo signaling pathway is a critical regulator of cell proliferation, organ size, and tissue homeostasis. It is regulated by a kinase cascade involving MST1/2 and LATS1/2 kinases, along with downstream transcriptional coactivators YAP and TAZ. This pathway acts as a tumor suppressor by inhibiting excessive cell growth and promoting apoptosis when necessary.

Under normal circumstances, MST1/2 kinases activate LATS1/2 kinases, which phosphorylate YAP and TAZ. Phosphorylated YAP/TAZ are sequestered in the cytoplasm or degraded, preventing them from entering the nucleus and activating TEAD transcription factors. This suppresses the expression of genes that promote cell proliferation and survival.

However, in many cancers, the Hippo pathway is inactivated. This leads to dephosphorylation of YAP/TAZ, which then translocate into the nucleus and bind TEADs to activate oncogenic gene expression. Additionally, repressors may inactivate MST/LATS kinases, further enhancing YAP/TAZ nuclear activity. The resulting unchecked activation of TEADs by dephosphorylated YAP/TAZ drives tumorigenic processes including increased proliferation, metastasis, and drug resistance.

Therefore, the situations that support cancer progression are:

(C) Activation of TEADs by dephosphorylated YAP/TAZ

(D) Inactivation of MST / LATS by repressors

Thus, the correct option is:

(3) C and D

Understanding these mechanisms is crucial for devising new cancer therapies targeting the Hippo pathway to restore its tumor-suppressive functions or inhibit oncogenic YAP/TAZ activity.

Answer: (3) C and D